Evidence for the presence of peroxisome proliferator-activated receptor (PPAR) alpha and gamma and retinoid Z receptor in cartilage. PPARgamma activation modulates the effects of interleukin-1beta on rat chondrocytes.

Peroxisome proliferator-activated receptor (PPAR) alpha, PPARgamma, and retinoid acid receptor-related orphan receptor (ROR) alpha are members of the nuclear receptor superfamily of ligand-activated transcription factors. Although they play a key role in adipocyte differentiation, lipid metabolism, or glucose homeostasis regulation, recent studies suggested that they might be involved in the inflammation control and especially in the modulation of the cytokine production. This strongly suggests that these transcriptional factors could modulate the deleterious effects of interleukin-1 (IL-1) on cartilage.

Pefloxacin-induced achilles tendon toxicity in rodents: biochemical changes in proteoglycan synthesis and oxidative damage to collagen.

Despite a relatively low incidence of serious side effects, fluoroquinolones and the fluoroquinolone pefloxacin have been reported to occasionally promote tendinopathy that might result in the complication of spontaneous rupture of tendons. In the present study, we investigated in rodents the intrinsic deleterious effect of pefloxacin (400 mg/kg of body weight) on Achilles tendon proteoglycans and collagen. Proteoglycan synthesis was determined by measurement of in vivo and ex vivo radiosulfate incorporation in mice.

[Non-steroidal anti-inflammatory drugs with selectivity for cyclooxygenase-2 in Alzheimer's disease. Rationale and perspectives].

POSSIBLE INFLAMMATORY MECHANISMS: Alzheimer's disease (AD) is a degenerative disease of the brain including possibly inflammatory mechanisms, as illustrated by the presence of activated microglial cells in the periphery of senile plaques and neurofibrillary tangles and the subsequent release of proinflammatory mediators with neurotoxic potency. RATIONALE FOR NSAID USE: Although not firmly demonstrated, the rationale for the prescription of non steroidal anti-inflammatory drugs (NSAIDS) as neuroprotective agents in AD lies on epidemiological data having shown a reduced risk of developing AD in patients on long-term therapy with NSAIDs (non selective cyclo-oxygenase [COX] inhibitors). RATIONALE FOR THE USE OF SELECTIVE COX-2 INHIBITORS: The rationale for the prescription of selective COX-2 inhibitors as neuroprotective drugs in AD lies on: Epidemiological data having shown a reduced risk of developing AD in patients treated with anti-inflammatory doses of classical NSAIDs (inhibition of COX-1 and COX-2) but not with antithrombotic doses of aspirin (selective inhibition of COX-1), Cellular experiments, Demonstration of a better gastro-intestinal (GI) safety profile with selective COX-2 inhibitors than with classical NSAIDs in short-term studies, allowing a possible long-term use in AD.

[Selective cyclooxygenase-2 (COX-2) inhibitors: importance and limitations].

The discovery of an inducible form of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase activity explains both therapeutic effects and side-effects of non-steroidal anti-inflammatory drugs (NSAIDs). Selective COX-2 inhibitors have demonstrated in clinical trials a significantly better gastrointestinal tolerability than classical NSAIDs, for the same anti-inflammatory activity. Their tolerability in patients with active ulcer or with a recent history of ulcer as well as in patients suffering from cardiovascular or renal diseases has still to be investigated in detail.

In vitro stereoselective degradation of carprofen glucuronide by human serum albumin. Characterization of sites and reactive amino acids.

Acyl glucuronides formed from carboxylic acids can undergo hydrolysis, acyl migration, and covalent binding to proteins. In buffers at physiological pH, the degradation of acylglucuronide of a chiral NSAID, carprofen, consisted mainly of acyl migration. Acidic pH reduced hydrolysis and acyl migration, thus stabilizing the carprofen acyl glucuronides.

Upright posture influences salivary cortisol.

This study was designed to investigate the influence of posture on salivary cortisol concentrations in healthy volunteers. In a balanced cross-over design 24 subjects were exposed at 1 week intervals to different body positions (sitting [S], lying [L] upright [U]) for 20 min in each condition. Before, during and after the experimental treatment measures of blood pressure, heart rate and saliva samples for determining the free fraction of cortisol were obtained.

Endocrine responses after d-fenfluramine and ipsapirone challenge: further support for Cloninger's tridimensional model of personality.

The tridemensional model of personality introduced by Cloninger relates aspects of novelty seeking to the dopaminergic, harm avoidance (HA) to the serotonergic, and reward dependence to the noradrenergic neurotransmitter system. Using a neuroendocrine challenge paradigm, this study investigates whether subjects characterized by blunted cortisol (CORT) responses after ipsapirone (IPS) relate to different subfactors of HA from those characterized by blunted prolactin (PRL) responses after treatment with d-fenfluramine (D-FEN). Moreover, subjects blunted in both responses should differ in scale values of subfactors of HA from those with only one or no blunted reactions.

Proteoglycan and collagen biochemical variations during fluoroquinolone-induced chondrotoxicity in mice.

Although fluoroquinolone antibacterials have a broad therapeutic use, with a relatively low incidence of severe side effects, they have been reported to induce lesions in the cartilage of growing animals by a mechanism that remains unclear. This study was undertaken to determine the potentially deleterious effect of a high dose of pefloxacin (400 mg/kg of body weight) on two main constituents of cartilage in mice, i.e.

Mobilization of lead from bone in end-stage renal failure patients with secondary hyperparathyroidism.

Background: It is now recognized that long-term exposure to even low levels of lead may increase bone lead content. Lead can then be released in toxicologically significant amounts during critical states of increased bone turnover.

Methods: Two patients with end-stage renal failure, one on haemodialysis and the other on continuous ambulatory peritoneal dialysis (CAPD), had been exposed to lead and developed secondary hyperparathyroidism.

Cartilage protection by nitric oxide synthase inhibitors after intraarticular injection of interleukin-1beta in rats.

Objective: To evaluate the effect of nitric oxide synthase (NOS) inhibitors on proteoglycan synthesis following intraarticular administration of interleukin-1beta (IL-1beta) in rats.

Methods: Recombinant human IL-1beta and NOS inhibitors with different selectivity for inducible NOS (N-monomethyl-L-arginine [L-NMA], N-iminoethyl-L-ornithine [L-NIO], and S-methylisothiourea [SMT]) were simultaneously administered in rats by a single intraarticular injection in each knee. L-NMA was also infused for 72 hours using an Alzet mini osmotic pump implanted into the peritoneal cavity 24 hours before IL-1beta challenge.

Evidence for neurogenic transmission inducing degenerative cartilage damage distant from local inflammation.

Objective: To investigate involvement of the nervous system in ipsilateral and contralateral joint inflammation.

Methods: Freund's complete adjuvant (CFA; 1 mg or 1 microg) was injected unilaterally and the messages (a) from the hind paw to the ipsilateral and contralateral knees and (b) from one knee to the contralateral knee were analyzed. The degenerative impact of the local injury on distant cartilage was assessed using patellar proteoglycan synthesis as an indicator.

Glycation of human serum albumin by acylglucuronides of nonsteroidal anti-inflammatory drugs of the series of phenylpropionates.

The covalent binding to human serum albumin (HSA), of acylglucuronides from carboxylic nonsteroidal anti-inflammatory drugs (NSAIDs) was investigated. The adduct formation was followed and quantitated by HPLC and by radiometric detection. Three types of albumin adducts were evidenced.

Biotelemetry: an original approach to experimental models of inflammation.

Biotelemetry is a new biological technology which evaluates continuous spontaneous locomotor activity and body temperature in rodents. The telemetry system comprises a transmitter implanted in the peritoneal cavity of the rodent, and a receiver placed beneath the animal's cage. The receiver detects the radio waves and the activity of the rodents as counts which are registered in the computer system, and the adapter detects the calibrated body temperature.

Changing psychobiological stress reactions by manipulating cognitive processes.

This study aimed at manipulating psychobiological reactions to public speaking stress by means of verbal comments during the anticipation period. Sixty male students were instructed to give a public talk in 10 min. Twenty subjects each were randomly assigned to one of three experimental conditions: During anticipation of the speech the experimenter remained silent in the control condition, gave feedback that the subject was physiologically aroused and nervous in the second (arousing manipulation), or that he was physiologically calm and relaxed in the third condition (reassuring manipulation).

Modulation of IL-1 effects on cartilage by NO synthase inhibitors: pharmacological studies in rats.

Objective To compare the ability of L-arginine (L-arg) analog nitric oxide synthase (NOS) inhibitors and isothioureas to restore the interleukin-1 (IL-1) induced inhibition of proteoglycan (PG) synthesis in rat.Methods Chondrocytes beads and patellae were challenged with IL-1betain vitro and monitored for NO production and proteoglycan synthesis. Rats injected with IL-1beta in knee joints were monitored for NO(2)( - )+NO(3)( - )levels in joint tissues and ex-vivo(35)S sulfate incorporation in patellae.

Mechanisms of apomorphine cytoxicity towards rat glioma C6 cells: protection by bovine serum albumin and formation of apomorphine-protein conjugates.

Apomorphine cytotoxicity towards rat glioma C6 cells was recently demonstrated to be time- and concentration-dependent. In the present work, the mechanism of cytotoxicity of apomorphine was further studied in the C6 cell line. We showed that bovine serum albumin partially protects C6 cells against apomorphine cytotoxicity.

Hyaluronate-alginate gel as a novel biomaterial: mechanical properties and formation mechanism.

With the aim of producing a biomaterial for surgical applications, the alginate-hyaluronate association has been investigated to combine the gel-forming properties of alginate with the healing properties of hyaluronate. Gels were prepared by diffusion of calcium into alginate-hyaluronate mixtures, with an alginate content of 20 mg/mL. The hyaluronate source was shown to have significant effect on the aspect and the properties of the gels.

Psychobiological differences between the aggression and psychoticism dimension.

Since blunted prolactin (PRL) and partly blunted cortisol responses have been reported for subjects with aggressive impulsive disorders as well as with psychopathy, it seemed worthwhile to try to separate the two types of aggression by their biological response. Since, furthermore, cortisol responses are more readily elicited by 5-HT1a challenges and prolactin responses by d-Fenfluramine or uptake inhibitors, these two types of drugs were used to answer the question if these hormone responses are suitable to differentiate between the two types of aggression. Two studies were conducted, one using 15 mg of d-Fenfluramine (d-Fen) in a double-blind placebo-controlled cross-over design in 40 males, the other using 10 mg of Ipsapirone (Ips) and placebo comparing 20 healthy males in each group.

The fibromyalgia syndrome as a manifestation of neuroticism?

After elucidating the components and theory of neuroticism (N) as well as of psychosomatic complaints and their relationships to personality dimensions and to psychosomatic diseases, comparisons are performed between patients suffering from fibromyalgia syndrome (FMS) or related pain diseases with healthy subjects scoring high on personality dimensions related to neuroticism. FMS and pain patients score high on depression, anxiety, and experience of stress although questionnaire scores on depression are higher in subjects not exhibiting somatic features of the disease. High subjective pain sensitivity and low thresholds for pain perception are also common features in high N subjects and FMS patients.

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.

Hyaluronate-alginate combination for the preparation of new biomaterials: investigation of the behaviour in aqueous solutions.

With the aim of producing a biomaterial for surgical applications, the alginate-hyaluronate association has been investigated. Crossed techniques were used to assess the existence of polymer interactions in aqueous solutions up to 20 mg/ml. Alginate was obtained from algae and hyaluronate was purified from rooster comb.

Separation and quantification by ion-association capillary zone electrophoresis of unsaturated disaccharide units of chondroitin sulfates and oligosaccharides derived from hyaluronan.

An analytical method has been developed for assay of unsaturated disaccharides of chondroitin sulfates and of oligosaccharides (tetra- and hexasaccharides) of hyaluronan, using ion-association capillary zone electrophoresis. Samples were applied at the anode (the usual polarity), using a borate buffer modified by an ion-pairing reagent, tetrabutylammonium (TBA) phosphate, and the effect of the concentration of the ion-pairing reagent on various electrophoretic parameters (electroosmotic flow, electrophoretic mobility of products, capacity factors) was observed. Increasing concentrations of the reagent led to a decrease of zeta potential, probably due to specific adsorption of the quaternary ammonium ion onto the capillary wall.

[Cell adhesion molecules and pharmacologic applications. Round Table No 3 at Giens XIII].

This workshop intended to perform a "state-of-the art" of current research on adhesion molecules in various pathophysiologies, and to determine pharmacological targets. Indeed, recent important progress concerning the cellular and molecular physiology of adhesion molecules led to the development of various integrin antagonists in several domains, like cardiovascular disease, inflammation and cancer. Integrins play a major role in numerous process like embryonic development, tumor growth and metastasis, apoptosis, hemostasis, leucocyte recruitment and activation, and bone resorption.