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Biomedical subjects

Y Henrotin

Publications and source records attributed to Y Henrotin.

At least 37 records · Page 2Linked to original sources

[Pharmacy clinics. How I treat...arthritis. First part: pathophysiologic recurrence and symptomatic treatment].

Osteoarthritis is now considered in all developed countries as a major burden for public health. During several years, the pharmacological management of osteoarthritis mainly focused on symptoms relief without interaction with the long-term structural progression of this disease. Based on recently published consensus, the present article summarizes the currently available options in the symptom-modifying management of osteoarthritis.

Anti-Inflammatory Agents, Non-Steroidal↗

[Biochemical mediators of inflammation].

Inflammatory processes are the physiological response of the organism to different stimuli such as trauma, infections or immunological reactions. The events leading to inflammation are characterized by leukocytes adhesion to the endothelium, diapedesis and migration, cells activation and tissue remodelling. These processes are initiated and regulated by a great variety of inflammatory mediators including cytokines, prostanoids, leukotrienes, neuropeptides, reactive oxygen and nitrogen species, complement components, coagulation factors and metalloproteases. This paper is devoted to the description of the major local effects of these mediators in the inflammatory reaction.

Blood Coagulation Factors↗

[What is the role of aceclofenac in the therapeutic arsenal against chronic osteoarthritis pathologies?].

The aim of this article is to critically review the potential role of aceclofenac in the treatment of inflammatory pain and chronic osteoarticular disorder, based on its activity on the mediators of inflammation, its effect on cartilage remodeling and on the results of clinical studies comparing aceclofenac with other NSAIDs in these disorders. Aceclofenac has an outstanding anti-inflammatory profile, involving besides a classical inhibition of prostaglandins E2, a decrease in the expression of several cytokines including interleukin 1 and tumor necrosis factor alpha. It also inhibits activated oxygen species production and influences cells adhesion. Aceclofenac and its main metabolite, 4-hydroxyaceclofenac, has positive effects on cartilage anabolism combined with modulating effect of matrix catabolism. Clinically, aceclofenac has been consistently shown to have a similar efficacy than that of widely marketed NSAIDs and a tolerance profile at least as good, if not better than the profile observed for other NSAIDs in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. As of today, no head to head comparison between aceclofenac and coxibs have been performed, nor for efficacy neither for tolerance. The specific profile of aceclofenac makes this NSAID an interesting candidate for long-term treatment of chronic rheumatic disorders as well as for treatment of acute inflammatory episodes.

Anti-Inflammatory Agents, Non-Steroidal↗

Evidence of nutriceutical effectiveness in the treatment of osteoarthritis.

Several entities have been carefully investigated for the symptomatic and structural management of osteoarthritis. The most compelling evidence of a potential for inhibiting the structural progression of osteoarthritis has been obtained with glucosamine sulfate, while some preliminary results also suggest that chondroitin sulfate could be used in the same indication. At any rate, these two compounds have clearly demonstrated a symptomatic action, mainly in osteoarthritis of the lower limbs. Symptomatic effect on pain relief and improvement of functional disability was also reported with the use of avocado/soybean extracts. Other nutriceuticals, including ginger extracts, should be more extensively investigated. An important issue is that all the conclusive studies with such chemical entities resulted from the use of prescription medicines, and not over-the-counter pills or food supplements.

Chondroitin Sulfates↗

Recent advances in inducible cyclooxygenase (COX-2) inhibition.

Cyclooxygenase is the key enzyme in the biosynthesis of prostanoids, biologically active substances that are involved in several physiological processes but also in pathological conditions such as inflammation. Since ten years now, it is well known that this enzyme exists under two forms: a constitutive (COX-1) and an inducible form (COX-2). Both enzymes are sensitive to inhibition by conventional nonsteroidal anti-inflammatory drugs (NSAIDs). Observations that COX-1, involved in several homeostatic processes, played a housekeeping role while COX-2 expression was associated with inflammation and other pathologies such as cancer proliferation have led to the development of COX-2 selective inhibitors in order to reduce the classical side-effects, of which gastric irritation is the most common, associated with the use of conventional NSAIDs.

Animals↗

Promising new agents in osteoporosis.

Currently marketed inhibitors of bone resorption or stimulators of bone formation have significantly contributed to a better preventive and therapeutic approach to postmenopausal and senile osteoporosis. However, none of the available compounds has unequivocally demonstrated an ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once the disease is established. Therefore, several new medications are being developed, with the aim of providing a better risk-benefit profile and/or a more favourable cost-utility assessment than available drugs. Potential inhibitors of bone resorption include specific inhibitors of the osteoclast's proton pump, inhibitors of prostaglandins or nitric oxide donors. Stimulators of osteoblastic activity and subsequent bone formation might be obtained by strontium salts, peptides of the parathyroid hormone family, growth hormone and insulin-like growth factors or bone morphogenetic proteins. Most of these compounds are now undergoing phase II/III development programmes, and results evaluating their potential benefit should be available within 1 to 5 years.

Animals↗

Production of active oxygen species by isolated human chondrocytes.

The ability of isolated human chondrocytes to produce active oxygen species has been investigated. The two methods for determining H2O2 and hydroxyl radicals (.OH) production were, by a fluorimetric method (production of dichlorofluorescein from a precursor in the presence of horseradish peroxidase and H2O2) and by a chromatographic method (measurement of ethylene production from gamma-methiol-keto-butyric acid after .OH attack). Chondrocytes were tested, both with and without activation by phorbol myristate acetate (PMA: 10(-6) M), in the presence of Ca2+ (1 x 10(-4) M) and Mg2+ (2 x 10(-4) M) or after variable periods of anoxia under nitrogen (4 to 12 h) followed by reoxygenation (with 95% O2, 5% CO2). Under these experimental conditions, the PMA-excited chondrocytes produced from 80 to 180 nmol of hydrogen peroxide per 1 x 10(6) cells and chondrocytes subjected to anoxia-reoxygenation produced up to 1700 nmol H2O2 per 1 x 10(6) cells. The hydroxyl radical production by PMA or anoxia-reoxygenation excited cells reached 600% of the production of non-excited cells and 1300% when they were subjected to successive stimulations by PMA and anoxia-reoxygenation. The possible pathological significance of these observations is discussed. The results indicate that stimulated human chondrocytes are capable of producing active oxygen species which could play a major role in joint inflammation and cartilage damage.

Adolescent↗

Active oxygen species, articular inflammation and cartilage damage.

Rheumatoid arthritis and osteoarthritis are age-related diseases, in which degenerative changes (arthrosis) and superimposed inflammatory reactions (arthritis) lead to progressive destruction of the joints. Active oxygen species derived from various sources play a role in this process, which may be influenced by appropriate treatment with antioxidants and free radical scavengers.

Aging↗

Effects of sodium naproxen on differentiated human chondrocytes cultivated in clusters.

The effects of different pharmacological concentrations of the non-steroidal anti-inflammatory drug (NSAID) sodium naproxen (NAP) were tested on several metabolic functions of differentiated human chondrocytes cultivated in clusters and compared with the action of acetylsalicylic acid (ASA). DNA synthesis was significantly inhibited by ASA but not by NAP. Proteoglycan production was also markedly decreased by ASA, while synthesis of type II collagen was not modified. By contrast, NAP did not affect these chondroformative processes. Both NSAIDs were potent inhibitors of prostaglandin E2 production. These results indicate that in terms of the parameters tested NAP does not lead to deleterious effects on human articular chondrocytes cultured in vitro.

Aspirin↗

In-vitro evaluation of drugs proposed as chondroprotective agents.

Three proposed chondroprotective agents (CP), namely glucosamine sulfate (GAS), chondroitin sulfate (CS) and glycosaminoglycan-peptide complex (GP-C), were tested on differentiated human articular chondrocytes cultured in clusters. Chondrocyte productions of proteoglycans (PG), type II collagen (coll. II) and prostaglandin E2 (PGE2) were established by specific radioimmunoassays applied to the culture medium (CM) and in chondrocyte clusters (CC). Collagenolytic activity was assayed in CM. DNA synthesis, studied by measuring 3H-thymidine incorporation, was unaffected by CS and GAS. GP-C, at low concentration, stimulated DNA synthesis. GP-C, at higher doses, induced a high increase in PG and coll. II productions. GAS and CS induced a stimulatory effect limited to PG production. None of the CP tested here affected the basal PGE2 production by human chondrocytes.

Cartilage, Articular↗

In vitro effects of Etodolac and acetylsalicylic acid on human chondrocyte metabolism.

The effects of two nonsteroidal anti-inflammatory drugs (NSAIDs), Etodolac (ETO) and acetylsalicylic acid (ASA), used at pharmacological concentrations, were tested on several metabolic parameters of human chondrocytes cultivated in three-dimensional culture. The results indicated that proteoglycan synthesis was significantly decreased by ASA treatment, whereas Etodolac did not affect this parameter. Neither ASA nor Etodolac modified type-II collagen production. Both NSAIDs were potent inhibitors of PGE2 production, but Etodolac was more efficient at equimolar concentrations. In contrast, collagenolytic activity was unaffected by Etodolac.

Anti-Inflammatory Agents, Non-Steroidal↗

Radioimmunoassay for human type II collagen.

Human articular cartilage type II collagen (h coll.II) was purified and used to develop a radioimmunoassay. The sequential saturation procedure allowed a sensitivity of 3 ng/tube. The intra and between assay coefficients of variation were less than 10 and 20% respectively in the linear part of the curve. The assay was highly specific for native human articular type II collagen. There was no cross-reactivity with other constituents of cartilage: human proteoglycans, fibronectin, laminin and hyaluronic acid did not interfere with the assay. No cross-reactivity existed with bovine collagen types I, III, IV. However, native collagens from human placenta (I, III, IV, V, VI), rat and calf skin type I collagens and bovine type II collagen produced a weak cross-reaction only at high doses. Concerning the latter, inhibition curves were not parallel. Parallelism of inhibition curves were observed for dilution of type II collagen, produced by human chondrocytes in three-dimensional culture. All of these characteristics indicate that radioimmunoassy of type II collagen is a very sensitive and specific method available for the study and quantification of type II collagen in in vitro experimental conditions.

Cartilage, Articular↗

In vitro assays of chondrocyte functions: the influence of drugs and hormones.

Human articular chondrocytes may be cultured in three dimensions, according to a method already validated. This model allows us to study the repair processes of the cartilage, by measuring the proliferative activity of chondrocytes and the synthesis of two major constituents of matrix: proteoglycans and type II collagen. Some substances are characterised by stimulatory effect on DNA synthesis and no effect or a defective effect on matrix components: this is the case for Epidermal Growth Factor. Others are able to stimulate (hGH) or to depress (acetyl salicylic acid) both chondrocyte proliferation and matrix components synthesis. Finally, some substances called "chondroprotective", such as the glycosaminoglycan-peptide complex, GP-C (Rumalon) stimulate either the proliferative response or the synthesis of proteoglycans and type II collagen, according to the dose.

Anti-Inflammatory Agents, Non-Steroidal↗

Effects of etodolac on human chondrocytes cultivated in three dimensional culture.

Human chondrocytes in three-dimensional culture were incubated for up to 20 days in the presence of etodolac, a nonsteroidal anti-inflammatory drug which penetrates readily into the synovial fluid. Even at an etodolac concentration of 80 micrograms/ml, DNA synthesis, proteoglycan synthesis, and type-II collagen synthesis were unchanged. Collagenase production was also unaffected by etodolac (60 micrograms/ml). In contrast, prostaglandin E2 production was reduced by 84% in the presence of 60 micrograms/ml of etodolac. The 80 micrograms/ml concentration is 5 times that found in the serum of subjects treated with 200 mg of etodolac twice a day for 6 days, and 33 times the concentration in synovial fluid of arthritic patients treated with etodolac 200 mg twice a day for 7 days. These in vitro results indicate that anti-inflammatory levels of etodolac may not damage articular cartilage in vivo.

Anti-Inflammatory Agents, Non-Steroidal↗

Effects of human and salmon calcitonin on human articular chondrocytes cultivated in clusters.

The effects of different pharmacological concentrations (0, 5, 10, 100, and 1000 ng/mL) of synthetic human calcitonin (hCT) and salmon calcitonin (sCT) on the incorporation of [3H]thymidine and production of proteoglycans (PG) and type II collagen (coll II) by human articular chondrocytes during a 20-day period were studied in a tridimensional chondrocyte culture model. [3H]Thymidine uptake was measured in chondrocyte clusters, and specific PG and coll II RIAs were performed every 4 days on the culture medium and cell aggregates; total PG and coll II production were also assessed at different culture durations by adding the amounts found in culture media and their corresponding clusters. Incubation with hCT or sCT did not affect [3H]thymidine uptake regardless of the dose. For each culture period, PG and coll II release into culture medium, cluster content, and total production increased significantly in a dose-dependent manner. Cumulative curves for these parameters showed a progressive significant increase with culture duration at hCT and sCT doses of 0, 5, and 10 ng/mL. Cumulative curves obtained with 10, 100, and 1000 ng/mL were seldom significantly different from one another. No differences emerged between the use of hCT or sCT. Thus, CT exerted no proliferative effect on human articular chondrocytes in tridimensional culture, but displayed a dose-dependent and prolonged stimulatory effect on PG and coll II production. CT may possess chondroprotective properties in addition to its other known effects.

Animals↗