Search PubMed⌕ Search

Biomedical subjects

P Netter

Publications and source records attributed to P Netter.

At least 19 recordsLinked to original sources
PubMed1999

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. The gels have viscoelastic behaviour and the transient measurements carried out in creep mode could be interpreted through a Kelvin-Voigt generalised model: experimental data led to the steady state hardness and a characteristic viscosity of the gel. Gels prepared from Na rooster comb hyaluronate with weight ratio up to 0.50 have satisfactory mechanical properties, and fully stable gels are obtained after a few days; on the contrary, use of lower molecular weight hyaluronate led to loose gels for hyaluronate contents over 0.25. Gel formation was investigated by measurements of the exchange fluxes between the calcium chloride solution and the forming gel, which allowed thorough investigations of the occuring diffusion phenomena of water, calcium ion and hyaluronate. Strong interactions of water with hyaluronate reduce significantly the rate of weight loss from the gel beads and allows higher water content in steady-state gels. Calcium content in the gel samples could be correlated to the actual alginate concentration, whatever the nature and the weight ratio of hyaluronate.

Alginates↗
PubMed1999

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. Viscometry measurements using the capillary technique or the Couette flow, together with circular dichroism investigations, evidenced the moderate significance of interactions between the two polysaccharides in dilute solutions. In addition, the case of more concentrated solutions and containing 20 mg/ml alginate was approached by rheological measurements in the flow mode; the behaviour of the polymer associations appeared as a compromise between those of individual polysaccharides.

Alginates↗
PubMed1999

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. In each study subjects were divided according to above and below median aggression and psychoticism scores measured by questionnaire scales and combined into four groups defined by high and low aggression (Ag+/-) and psychoticism (P+/-) scores respectively. Analyses of covariance based an the two personality factors and the drug revealed for d-Fen cortisol nonresponse in P+ as opposed to P- and a blunted PRL response in Ag+ as opposed to Ag-. With Ips the cortisol response was positively related to Ag and not to P, while P+ showed a blunted PRL response not observed in Ag+. Joyfulness and well-being were also differentially affected by d-Fen in high and low P scorers, but not correlated to respective hormone responses. Different hypothalamic mechanism for eliciting the two hormone responses and differences in pre- and postsynaptic receptor sensitivities in the two personality dimensions are inferred from these findings.

Adult↗
PubMed1999

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↗
PubMed1998

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. The authors propose a mechanism of separation, in which anionic borate complexes are formed and interact with TBA ion inside the capillary tube. The capillary electrophoretic system described is potentially a powerful method for specific measurement of the concentrations in joint tissues of chondroitin 4-sulfate, chondroitin 6-sulfate, and hyaluronan, whose relative abundances may vary in various diseases or after local treatments with, for example, antiinflammatory drugs, chondroprotective agents, or orthopedic implants.

Chondroitin Sulfates↗
PubMed1998

Fluoride salts are no better at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis: the FAVOStudy.

Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density (BMD) in postmenopausal osteoporosis, the effects of this gain in density on the vertebral fracture rate remain controversial. We conducted a 2-year multicenter, prospective, randomized, double-masked clinical trial in 354 osteoporotic women with vertebral fractures (mean age 65.7 years). They received either fluoride (208 patients), given as sodium fluoride (50 mg/day) or as monofluorophosphate (200 mg/day or 150 mg/day), or a placebo (146 patients). All patients received daily supplements of 1 g of calcium (Ca) and 800 IU of vitamin D2 (D). A 1-year open follow-up on Ca-D was obtained in 124 patients. After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8% and 2.4% respectively (p = 0.0001). However, the rate of patients with at least one new vertebral fracture, defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89% of patients, was similar in the fluoride groups and the Ca-D group. No difference between the three fluoride regimens was found. The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups (1.9% and 1.4% respectively for hip fractures). A lower limb pain syndrome occurred more frequently in the fluoride groups. In the 124 patients followed for 1 year after cessation of fluoride therapy, the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group. We conclude that fluoride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis.

Aged↗
PubMed1998

Personality related effects of nicotine, mode of application, and expectancies on performance, emotional states, and desire for smoking.

Three separate factors relevant to nicotine effects have been investigated in this experiment in combination: the experimentally induced expectation about receiving a sham or a nicotine cigarette, the mode of application of nicotine by a tablet, by a cigarette or not at all, while the belief of receiving the nicotine via smoking was held constant in each condition (by nicotine or sham smoking), and the personality factors of extraversion or neuroticism, respectively. Ninety-six healthy female student smokers were tested in a 2 x 3 x 2 factorial group comparison design with respect to critical flicker fusion and reaction time performance as well as to self-ratings on emotional and cortical arousal and ratings on desire for further cigarettes (satisfaction from smoking a single cigarette containing either 0.8 mg nicotine or a sham cigarette). In each case, a tablet containing either nicotine or placebo was administered together with the cigarette. The results showed that performance is sensitive to interaction effects of instruction and mode of application. The instruction of sham or nicotine assignment when applied with a congruent treatment (sham with a sham cigarette, or nicotine with a nicotine cigarette) both increased performance, while groups with discordant information showed worse performance. The administration of nicotine by tablets or by smoking differs considerably, nicotine cigarettes causing a stronger increase in emotional arousal, tablets rather a decrease or no effect, while the true placebo condition increases arousal due to deprivation effects. This leads to an enhancement of the nicotine effect with real smoking and to reactive increase of effort when sham smoking. The instruction affects alertness, the nicotine illusion leading to a lower reduction in subjective reports of alertness and concentration than that observed with the sham instruction. Neurotic subjects become more anxious and tense with nicotine cigarettes than stable subjects. This effect is less pronounced or even reversed with tablets. No interactions with instructions are observed with neuroticism. Extraverts tend to show a decrease in performance but an increase in alertness with the instruction of receiving nicotine as opposed to the sham expectation, whereas introverts behave the opposite way. Subjective ratings on arousal seem to follow the law of transmarginal inhibition, with extraverts being pushed from low arousal to high and introverts vice versa by the mere expectation.

Adult↗
PubMed1998

Effect of dimethicone (polysilane gel) on the stereoselective pharmacokinetics of ketoprofen.

OBJECTIVE: Since dimethicone may be employed to improve gastrointestinal tolerability of non steroidal anti-inflammatory drugs (NSAIDs), we studied its influence on the pharmacokinetics of ketoprofen in subjects receiving a single oral dose of racemic ketoprofen. PATIENTS AND METHODS: In a cross-over experimental design, 12 healthy fasting volunteers were given a single oral dose (100 mg) of racemic ketoprofen, administered with or without dimethicone. The kinetic parameters measured were area under the concentration (AUC), maximum peak plasma concentration (Cmax), time to reach peak concentration (tmax), elimination half-life (t1/2), mean residence time (MRT) and urinary excretion for R and S enantiomers. RESULTS: Dimethicone reduced the peak concentration of both R and S ketoprofen by about 10% (P<0.05) and also induced a slight but non-significant increase in the mean time to achieve peak concentration. However, this treatment had no significant effect on the bioavailability and the elimination of R and S enantiomers, as shown by AUC, t1/2 and MRT values. The absorption patterns were equivalent for both ketoprofen isomers, since plasma pharmacokinetic parameters were similar. Nevertheless, the urinary recovery was significantly lower for R ketoprofen than for its antipode. The administration of dimethicone did not alter this stereoselectivity. CONCLUSION: The administration of dimethicone to alleviate the epigastralgic effects related to NSAIDs does not affect the efficacy of the treatment. Dimethicone did not significantly alter the bioavailability of ketoprofen, chosen as an example of an NSAID, especially that of the pharmacologically active S enantiomer.

Adult↗
PubMed1998

Molecular and biochemical analysis of Saccharomyces cerevisiae cox1 mutants.

We report on the molecular and biochemical analysis of a set of 13 respiratory deficient mutants of Saccharomyces cerevisiae which are specifically altered in COX1, the gene encoding the subunit Cox1p of cytochrome c oxidase. DNA sequence analysis shows that three are due to frameshift mutations, two to nonsense mutations, and eight to missense mutations. All, except the missense mutant S157L, have impaired electron transfer and respiratory activity. Analysis of the mitochondrial translation products shows that when Cox1p is absent, Cox2p and Cox3p are still synthesized. In the missense mutants, the steady state levels in the mitochondrial membranes of the three mitochondrially encoded subunits Cox1p, Cox2p and Cox3p and the nuclear-encoded subunit Cox4p are reduced. In the frameshift and nonsense mutants, Cox1p is absent and Cox2p, Cox3p and Cox4p are considerably decreased or undetectable. A comparison of the steady state levels of Cox1p through Cox4p in the COX1, COX2, COX3 and COX4 mutants shows the interdependance of the accumulation of these four subunits in the mitochondrial membranes.

Amino Acid Sequence↗
PubMed1998

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. On the endocrinological level cortisol responses to challenge tests with CRH as well as prolactin responses to TRH are higher in FMS patients than in high N healthy subjects indicating an endocrinological difference. A common feature, however, is the lack of adaptability in the two groups, since neurotics are in particular characterized by a low capacity to shift their behavior from one state to the other (waking-sleeping, working-relaxing), to re-adapt to baseline levels after endocrinological or physiological stress responses, or to adjust to conditions of shift work. This is reflected by chronobiological disturbances in FMS patients and could also explain their maintainance of pain perception, because they are incapable of correcting conditioned pain-producing muscle tension.

Adaptation, Psychological↗
PubMed1998

Evaluation of acoustical parameter sensitivity to age-related and osteoarthritic changes in articular cartilage using 50-MHz ultrasound.

The current study reports the sensitivity of acoustical parameters estimated at high frequency to the osteoarthritic morphological and structural changes in patellar cartilage in rat knees. Osteoarthritis (OA) was induced by a single intra-articular injection of mono-iodo-acetic acid in right knees. OA patellas and their contralateral controls were excised at regular intervals after injection and were examined in vitro with a scanning acoustical microscope operating with a poly(vinylidene di-fluoride) (PVDF) 80-MHz focused transducer. Cartilage thickness was estimated using B-scan images. The quantitative analysis of the radiofrequency signal backscattered by the cartilage was performed using integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB), which were estimated in the 20-60-MHz frequency range. One week after injection, a cartilage thickness decrease was detected (-6%, on average) that preceded the significant hypertrophy (20.1%) that occurred 2 weeks after injection and could be due to tissue repair. From 1 week to 3 weeks after injection, the IRC of OA patellas was significantly lower than that of control patellas. The IRC difference increased with time from -3.3 +/- 2.4 dB at 1 week to -8.4 +/- 1.7 dB at 3 weeks. An AIB decrease was observed with time for both OA and control patellas (-2.9 to -4.2 dB per week). An AIB difference between OA and control patellas was detected from 1 week to 3 weeks after injection. This difference decreased with time. IRC variation reflects a change in acoustical impedance of the superficial layer of the cartilage and could be linked to a change in constituent content and/or to a disruption of fibers of the collagen network that led to the fibrillation of the cartilage surface. AIB variation reflects a change in shape, size and/or density of the scatterers and could be related to changes in the constituent content and in the organization of the matrix in the internal layer of the cartilage. IRC and AIB could provide information about the structural modifications of the cartilage due to osteoarthritis or to cartilage maturation.

Aging↗
PubMed1998

Modulation of IL-1-induced cartilage injury by NO synthase inhibitors: a comparative study with rat chondrocytes and cartilage entities.

Nitric oxide (NO) is produced in diseased joints and may be a key mediator of IL-1 effects on cartilage. Therefore, we compared the potency of new [aminoguanidine (AG), S-methylisothiourea (SMT), S-aminoethylisothiourea (AETU)] and classical [Nomega-monomethyl-L-arginine (L-NMMA), Nomega-nitro-L-arginine methyl ester (L-NAME)] NO synthase (NOS) inhibitors on the inhibitory effect of recombinant human interleukin-1beta (rhIL-1beta) on rat cartilage anabolism. Three different culture systems were used: (1) isolated chondrocytes encapsulated in alginate beads; (2) patellae and (3) femoral head caps. Chondrocyte beads and cartilage entities were incubated in vitro for 48 h in the presence of rhIL-1beta with a daily change of incubation medium to obtain optimal responses on proteoglycan synthesis and NO production. Proteoglycan synthesis was assessed by incorporation of radiolabelled sodium sulphate [Na2(35)SO4] and NO production by cumulated nitrite release during the period of study. Chondrocytes and patellae, as well as femoral head caps, responded concentration-dependently to IL-1beta challenge (0 to 250 U ml(-1) and 0 to 15 U ml(-1) respectively) by a large increase in nitrite level and a marked suppression of proteoglycan synthesis. Above these concentrations of IL-1beta (2500 U ml(-1) and 30 U ml(-1) respectively), proteoglycan synthesis plateaued whereas nitrite release still increased thus suggesting different concentration-response curves. When studying the effect of NOS inhibitors (1 to 1000 microM) on NO production by cartilage cells stimulated with IL-1beta (25 U ml(-1) or 5 U ml(-1)), we observed that: (i) their ability to reduce nitrite level decreased from chondrocytes to cartilage samples, except for L-NMMA and AETU; (ii) they could be roughly classified in the following rank order of potency: AETU > L-NMMA > or = SMT > or = AG > or = L-NAME and (iii) AETU was cytotoxic when used in the millimolar range. When studying the effect of NOS inhibitors on proteoglycan synthesis by cartilage cells treated with IL-1beta, we observed that: (i) they had more marked effects on proteoglycan synthesis in chondrocytes than in cartilage samples; (ii) they could be roughly classified in the following rank order of potency: L-NAME > or = L-NMMA > > AG > SMT > > AETU and (iii) potentiation of the IL-1 effect by AETU was consistent with cytotoxicity in the millimolar range. D-isomers of L-arginine analog inhibitors (1000 microM) were unable to correct nitrite levels or proteoglycan synthesis in IL-1beta treated cells. L-arginine (5000 microM) tended to reverse the correcting effect of L-NMMA (1000 microM) on proteoglycan synthesis, thus suggesting a NO-related chondroprotective effect. However, data with L-NAME and SMT argued against a general inverse relationship between nitrite level and proteoglycan synthesis. Dexamethasone (0.1 to 100 microM) (i) failed to inhibit NO production in femoral head caps and chondrocytes beads whilst reducing it in patellae (50%) and (ii) did not affect or worsened the inhibitory effect of IL-1beta on proteoglycan synthesis. Such results suggested a corticosteroid-resistance of rat chondrocyte iNOS. Data from patellae supported a possible contribution of subchondral bone in NO production. In conclusion, our results suggest that (i) NO may account only partially for the suppressive effects of IL-1beta on proteoglycan synthesis, particularly in cartilage samples; (ii) the chondroprotective potency of NOS inhibitors can not be extrapolated from their effects on NO production by joint-derived cells and (iii) L-arginine analog inhibitors are more promising than S-substituted isothioureas for putative therapeutical uses.

Animals↗
PubMed1998

Personality correlates of +/- pindolol induced decreases in prolactin.

The present study was conducted to investigate if personality traits can be usefully related to serotonergic vs. dopaminergic action of the 5-HT1a-antagonist +/- pindolol. Forty healthy male volunteers (aged between 20 and 30 years) were randomly assigned to a placebo or a +/- pindolol (30 mg, oral dose) group in a double blind trial. Blood samples were drawn and analyzed for PRL concentrations. In addition, the subjects completed questionnaires on personality. The results indicated that +/- pindolol decreases PRL concentrations depending on personality. While subjects high on impulsivity and related traits (aggression and disinhibition) show lower PRL decreases, well-being and personality traits frequently related to dopaminergic activity were not correlated with changes in PRL. Since reduced (blunted) PRL-responses after 5-HT challenge tests have been reported for impulsives, the present results favor the involvement of primarily serotonergic and probably only secondarily dopaminergic control of +/- pindolol induced PRL decreases.

Adrenergic beta-Antagonists↗
PubMed1998

Changes in cortisol secretion during shiftwork: implications for tolerance to shiftwork?

The present study was conducted to determine the size of changes and the time point of those changes in biological rhythms during night-shift and whether they are associated with tolerance to shiftwork. The adrenal hormone cortisol has frequently been investigated in the field of shiftwork since it follows a pronounced circadian variation and has been demonstrated to be affected by night-work. However, studies are restricted with respect to sample size, number of measurements or duration of sampling periods. Therefore, a sample of 24 night-shift workers was investigated in a cardiac emergency unit for seven nights. Saliva samples were collected frequently for determination of cortisol. A total of 28 cortisol measurements in each subject were made in order to decide whether the circadian rhythm changed, and if so at which time point. A clear reversal of circadian function could be observed for the total group (mean cortisol concentrations) after the fifth night. However, inspection of individual patterns revealed that six out of 24 subjects did not change in circadian function. These subjects exhibited lower durations of and less consistency in recovery sleep across the following days after night-work. With respect to personality dimensions a pattern associated with neuroticism can be observed in subjects without appropriate changes in cortisol rhythm. However, owing to the small sample size of non-adapters these results are preliminary and should be replicated with larger samples. The overall relationship between neuroticism and low adaptability has been discussed.

Adaptation, Physiological↗
PubMed1998

Amyloid and non-amyloid carpal tunnel syndrome in patients receiving chronic renal dialysis.

OBJECTIVE: To determine the prevalence of amyloid deposits among patients with carpal tunnel syndrome (CTS) receiving dialysis, and to investigate the factors associated with amyloid and non-amyloid CTS. METHODS: Subjects for this prospective study were dialysis patients who underwent surgery for CTS in the same surgical unit between 1989 and 1997. CTS was diagnosed from clinical and electromyographic (EMG) findings. Systematic standard radiographs and laboratory data were also obtained. Surgical investigations included systematic macroscopic examination and biopsy of the epineurium, flexor retinaculum, synovium, and flexor tendon sheaths. Samples were stained for amyloid and examined by plain and polarized light microscopy, immunohistochemistry, and electron microscopy. RESULTS: Forty-one samples from 30 patients (11 bilateral cases) were examined. Amyloid deposits were found in 26 samples from 18 patients (7 M, 11 F). Fifteen samples from 12 patients (3 M, 9 F) showed no amyloid deposits. Amyloid CTS was statistically significantly associated with arthralgia and longterm dialysis [mean 13.3 (range 5.5-23) vs 7.5 yrs (range 3 mo-14 yrs)] in non-amyloid CTS. Flexor tenosynovitis and carpal bone erosion occurred more frequently in amyloid CTS. There were no statistically significant differences between the 2 groups in clinical, laboratory or EMG findings, type of dialysis membrane, or frequency of ipsilateral fistula. Only amyloid CTS was recurrent. CONCLUSION: Amyloid deposits were confirmed microscopically in 63.4% of patients. The relatively large number of cases of non-amyloid CTS without signs of dialysis associated arthropathy suggests that CTS is not a satisfactory criterion for diagnosis of dialysis arthropathy or beta2-microglobulin amyloidosis unless the presence of amyloid has been confirmed or duration of dialysis treatment has been at least 15 years.

Adult↗
PubMed1997

Suppressors of cis-acting splicing-deficient mutations that affect the ribozyme core of a group II intron.

Many of the cis-dominant mutations that lead to respiratory deficiency by preventing maturation of specific yeast mitochondrial transcripts are found to affect the ribozyme core of group I and group II introns. We have searched for suppressors of mutations in the ribozyme-encoding sections of a group II intron, the first intron in the COX1 gene of Saccharomyces cerevisiae, which was independently subjected to in vitro site-directed mutagenesis. Three of the original mutants bore multiple mutations, which act synergistically, since for most individual mutations, suppressors could be obtained that ensured at least partial recovery of respiratory competence and splicing. Out of a total of ten suppressor mutations that were identified, three were second-site substitutions that restored postulated base-pairings in the ribozyme core. Remarkably, and as is observed for group I introns, at least half of the cis-dominant mutations in the first two group II introns of the COX1 gene affect sites that have been shown to participate in RNA tertiary interactions. We propose that this bias reflects cooperativity in the formation of ribozyme tertiary but not secondary structure, on the one hand, and the need for synergistic effects in order to generate a respiratory-deficient phenotype in the laboratory on the other. Finally, a novel in vivo splicing product of mutant cells is attributed to bimolecular splicing at high concentrations of defective transcripts.

Base Sequence↗
PubMed1997

Mono-iodoacetate-induced experimental osteoarthritis: a dose-response study of loss of mobility, morphology, and biochemistry.

OBJECTIVE: To characterize the dose-responsiveness of morphologic and biochemical chondral changes relative to mobility in mono-iodoacetate (MIA)-induced osteoarthritis (OA) in rats. METHODS: Rat mobility was assessed by biotelemetry. Articular lesions were characterized by macroscopic and histologic examinations. Cartilage proteoglycan metabolism was evaluated by the 1,9-dimethylmethylene blue dye binding assay and by radiosulfate incorporation in patellar cartilage. RESULTS: Spontaneous locomotor activity was rapidly, transiently, and dose-dependently decreased after MIA injection into rat knees (primary response). Thereafter, only high doses (0.3 mg and 3.0 mg) led to a secondary progressive long-term loss of spontaneous mobility on day 15, when subchondral bone was exposed. These 2 doses resulted in significant changes in cartilage proteoglycan concentration at day 15 and a strong inhibition of anabolism in the peripheral patellae by day 2, contrasting with the effects of lower doses (0.01, 0.03, and 0.1 mg). CONCLUSION: When a sufficient dose of MIA is used, this model can easily and quickly reproduce OA-like lesions and functional impairment in rats, similar to that observed in human disease. These parameters, as well as proteoglycan metabolism, could serve as indicators for studying chondroprotective drugs, or for evaluating the ability of imaging techniques to detect and evaluate chondral lesions.

Animals↗