Search PubMed⌕ Search

Biomedical subjects

P Netter

Publications and source records attributed to P Netter.

At least 55 records · Page 3Linked to original sources
PubMed1997

In vitro magnetic resonance microimaging of experimental osteoarthritis in the rat knee joint.

OBJECTIVE: To visualize articular changes during iodoacetate induced osteoarthritis (OA) of the rat knee using high resolution magnetic resonance imaging (MRI). METHODS: All images were acquired on a 8.5T microimager on ex vivo rat knees. After optimization studies, 3D spin echo sequences were used with TR 1200 ms and TE 15 ms; 40 sagittal images were obtained with a resolution of 400 x 60 x 60 microns. OA lesions were achieved by injecting 3 mg iodoacetate in the right knee joint (Day 0). Progression of OA changes was studied at Days 5, 10, 15, 20, 30, 90 and corresponding radiographs and histological sections were obtained. RESULTS: Spin echo images of the normal rat knee clearly visualized cortical bone, calcified menisci, patella, and cruciate ligaments as dark regions. Cartilage and muscles appeared as intermediate signal. In some cases a trilaminar appearance of cartilage and growth plate was depicted. This appearance persisted at Day 5, although cartilage presented a marked loss of proteoglycans. After Day 10 the menisci appeared irregular and inhomogeneous. After Day 15, MRI showed important alterations of articular cartilage, predominant on weight bearing areas of femoral condyles. Osteophytic remodeling was also seen around the patella. From Day 20 to Day 90 anatomical changes progressively affected epiphyseal bone, leading to subchondral cysts and loss of its regular trabecular structure. CONCLUSION: High field MRI provides a sensitive method for investigating ex vivo focal erosions of cartilage and established osteochondral remodeling in experimental OA in the rat. In this model, microimaging provides more information about early modifications of cartilage and soft tissue than radiographic exploration, in good correlation with histological data.

Animals↗
PubMed1996

Sequence of a 39,411 bp DNA fragment covering the left end of chromosome VII of Saccharomyces cerevisiae.

We have sequenced a DNA fragment of 39,411 bp which includes part of the left telomere of chromosome VII of Saccharomyces cerevisiae. We have identified 19 open reading frames (ORFs); six correspond to known yeast genes (ADH4, FZF1, HKB, RTG2, HFM1 and PDE1), nine have similarity with other genes and four exhibit no significant similarity with any known gene. The average size of these ORFs seems to be related to their location, the eight ORF's nearest the telomere being shorter than the 11 others. These two groups of genes are separated by a region of 4.5 kb devoid of significant ORFs. One ORF, NRF120, is a new member of the seripauperine family, represented once in all sequenced yeast chromosomes, in a subtelomeric location.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Albumin binding sites for etodolac enantiomers.

Non-steroidal anti-inflammatory drugs (NSAIDs) are strongly bound to human serum albumin (HSA), mainly to sites I and II. The aim of this study was to characterize the binding site(s) of etodolac enantiomers under physiological conditions (580 microM HSA) using equilibrium dialysis. The protein binding of etodolac enantiomers, alone or in various ratios, was studied in order to evaluate the potential competition between them. Our results showed that (S)-etodolac was more strongly bound to HSA than (R)-etodolac. The displacement of one enantiomer by its antipode was observed only at high concentrations of the competitor, and was more pronounced for (S)-form. Displacement studies of the enantiomers by specific probes of sites I and II of albumin, dansylamide, and dansylsarcosine, respectively, showed that (R)-etodolac was slightly displaced by both these probes whereas the free concentration of (S)-etodolac increased markedly in the presence of dansylsarcosine. Moreover, the binding of ligands to sites I and II is usually affected by alkaline pH, by chloride ions, and by fatty acids. For etodolac, the presence of 0.1 and 1 M chloride ions and increasing pH (5.5-9) decreased the binding of both enantiomers. The same result was obtained with addition of octanoic acid. Conversely, the addition of oleic, palmitic, or stearic acid to the protein solution increased the binding of (R)-etodolac, but decreased that of its antipode. All these findings suggest (R)- and (S)-etodolac interact mainly with site II of HSA, and that the (R)-isomer is also bound to site I under physiological conditions.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Stereoselective distribution of tiaprofenic acid in synovium and cartilage in osteoarthritic patients.

OBJECTIVE: In order to document the stereoselective distribution in joints of a chiral nonsteroidal anti-inflammatory drug, the relative affinities of the enantiomers of tiaprofenic acid in synovium and for cartilage were compared. METHODS: The distribution of tiaprofenic acid in synovium and in cartilage was studied 25 h after administering the racemic drug for 2 days (600 mg of a sustained-release preparation, once daily), in 12 inpatients with osteoarthritis of the hip requiring arthroplasty. Enantiomers were quantified in plasma and freeze-ground tissues by a chiral HPLC assay. RESULTS: Plasma concentrations of the dextrorotatory (R) enantiomer (0.40 microgram/ml) were higher than those of its antipode. The concentration of racemate in synovium (in dried and fresh tissues, 150% and 40%, respectively, of the concentration in plasma) was much higher than that in cartilage (in dried tissues 32% of the plasma concentration). The ratio of the active, dextrorotatory (R) enantiomer to its antipode was higher in synovial tissue than in plasma. CONCLUSION: Tiaprofenic acid is distributed stereoselectively in plasma and synovium, which contain a higher concentration of the active, dextrorotatory (R) enantiomer. In cartilage, it reaches only a very low concentration.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Psychosocial stress in tree shrews: clomipramine counteracts behavioral and endocrine changes.

Male tree shrews (Tupaia belangeri) provide an animal model to study the neurobehavioral consequences of chronic psychosocial stress. When living in visual and olfactory contact with a male conspecific by which it has been defeated, the subordinante tree shrew shows dramatic behavioral, physiological, and neuroendocrine changes. Because the over all pattern of these changes resemble a depression-like symptomatology, we investigated to what extent the behavioral and endocrine changes in subordinate animals can be reversed by treatment with the tricyclic antidepressant clomipramine. In the present study, animals were subjected to a 10-day period of psychosocial conflict to elicit stress-induced behavioral and endocrine alterations before the onset of drug treatment, and psychosocial stress continued throughout the treatment period of 30 days. Clomipramine was administered orally once daily at a dose of 50 mg/kg. The drug had a time-dependent restorative influence on marking and grooming behavior, locomotor activity, risk assessment, as well as on urinary cortisol and norepinephrine excretion. It, thus, appears that the clomipramine treatment counteracts the behavioral and endocrine effects of chronic psychosocial stress in tree shrews, and the time course of recovery corresponds closely to that observed when treating depressed patients in the clinic.

Animals↗
PubMed1996

Evaluation of the effect of three surface treatments on the biocompatibility of 316L stainless steel using human differentiated cells.

AISI 316L stainless steel (SS) is widely used in orthopaedic implantology, although biological complications may result from its insufficient mechanical and tribological properties. In order to improve the wear and corrosion resistance as well as the hardness of 316L SS, three surface treatments, derived from those applied in mechanical engineering industries, were investigated: (1) glow discharge nitrogen implantation, (2) carbon-doped stainless steel coating sputtering and (3) low temperature plasma nitriding. Surface characterization according to the different heat treatments showed that corrosion and wear resistance were strongly improved, especially by ion implantation or carbon-doped SS coating sputtering. In the same way, microhardness was significantly increased after the three treatments. The effect of such treatments on the biocompatibility of 316L SS was studied with human osteoblast and fibroblast cultures. Basic and specific features of the cells showed that ion-implanted and carbon-doped stainless steels were biocompatible, whereas dramatic cellular reactions were noted when contacted with nitrided stainless steel. A hypothesis is given to explain this observation but further experiments are needed to optimize the nitriding process. Nitrogen implantation and carbon-doped layer deposition could be efficient means for improving the physical properties of stainless steel without affecting its biocompatibility. Such surface treatments may have relevance for increasing the life time of 316L biomedical devices.

Alkaline Phosphatase↗
PubMed1996

Cytocompatibility of Ti-6Al-4V and Ti-5Al-2.5Fe alloys according to three surface treatments, using human fibroblasts and osteoblasts.

Titanium alloys are well known for their superior mechanical properties as well as for their good biocompatibility, making them desirable as surgical implant materials. However, these alloys have been proven to behave poorly in friction since wear particles were often detected in tissues and organs associated with titanium implants. In this paper, three surface treatments were investigated in order to improve the wear resistance and the hardness of Ti-6Al-4V and Ti-5Al-2.5Fe: (a) glow discharge nitrogen implantation (10(17) atoms cm-2), (b) plasma nitriding by plasma diffusion treatment (PDT) and (c) deposition of TiN layer by plasma-assisted chemical vapour deposition (PACVD) additionally to PDT. Surface characterization after the different treatments showed considerable improvement in surface hardness, especially after the two nitriding processes. Moreover, the good corrosion resistance of untreated alloys was maintained. A cell culture model using human cells was chosen to study the effect of such treatments on the cytocompatibility of these materials. The results showed that Ti-5Al-2.5Fe alloy was as cytocompatible as the Ti-6Al-4V alloy and the same surface treatment led to identical biological consequences on both alloys. Nitrogen implantation did not modify at all the cellular behaviour observed on untreated samples. After the two nitriding treatments, cell proliferation and viability appeared to be significantly reduced and the scanning electron microscopy study revealed somewhat irregular surface states. However, osteoblast phenotype expression and protein synthesis capacity were not affected. PDT and PACVD may be interesting alternatives to the physical vapour deposition technique.

Alkaline Phosphatase↗
PubMed1996

5-HT agonist-induced changes in peripheral immune cells in healthy volunteers: the impact of personality.

The present study was conducted to investigate the relationship between the serotonergic neurotransmitter system and migration patterns of peripheral lymphocytes. Altogether 40 healthy male volunteers were given either a single dosage of the 5-HT1a-receptor agonist ipsapirone (10 mg) or a placebo (n = 20 each) in a double-blind randomized trial. Blood samples were drawn 55, 90 and 110 min after drug intake (baseline) and were analyzed for the number of peripheral lymphocytes. Furthermore, saliva samples were obtained at 13 defined time points which were analyzed for cortisol concentrations. Personality traits impulsivity, psychoticism and boredom susceptibility) were measured by questionnaires to investigate personality related differences in levels of serotonergic responsiveness. Analyses of covariance indicated that ipsapirone leads to highly significant reductions of peripheral CD4+ cells (T-helper/inducer-cells). This was significantly correlated to the ipsapirone-induced release of cortisol in a time-dependent manner. Furthermore, subjects scoring high on impulsivity, psychoticism and boredom susceptibility could be identified as being more responsive to the 5-HT agonist, indicated by their larger reduction in T-helper cells and greater cortisol release. This was hypothesized to be either due to their subsensitivity of presynaptic or supersensitivity of postsynaptic 5-HT1a-receptors.

Adult↗
PubMed1996

Local immunocompetence and salivary cortisol in confinement.

The present study describes the effects of a 60-day isolation period on the salivary levels of cortisol and secretory IgA. The study took place in the context of the EXEMSI project in which four volunteers were isolated in a space station-like chamber in the DLR Institute of Aerospace Medicine in order to examine the effects of long term isolation. Inspection of the individual immunoglobulin A secretion rates revealed different patterns of cyclic variation with respect to the weekday-weekend schedule, and different time lags for the adaptation leading to a plateau for this parameter. The salivary cortisol levels showed a circadian rhythm with high concentrations in the early morning (7:30 am) and lower concentrations in the late evening (11:00 pm). Moreover, in all subjects marked increases of salivary cortisol were observed in a 12- to 14-day cycle. In two subjects the marked morning-evening differences were only visible at the weekends. The salivary cortisol and immunoglobulin A levels were determined twice weekly before and after completion of a complex decision-making test. The results reveal a changed responsiveness in all subjects at different times.

Adult↗
PubMed1996

Serotonin and dopamine as mediators of sensation seeking behavior.

The purpose of the present paper was to investigate the relationship of the serotonergic and dopaminergic systems to subscales of sensation seeking (SS). Two of the subscales, Disinhibition (DIS) and Experience Seeking (ES), were chosen for analysis based on their representation of the two major factors obtained in a factor analysis: DIS represents a factor of lack of impulse control and ES a factor of novelty seeking. In studies 1 and 2 responsivity to a serotonergic (5-HT) challenge by a 5-HT1a receptor agonist (ipsapirone) was investigated by drug-induced prolactin (PRL) and cortisol responses, as well as by emotional states and behavioral measures. The dopaminergic (DA) response to a DA agonist (lisuride) and antagonist (fluphenazine) was analyzed in a condition of smoking deprivation (study 3) using PRL responses, emotional states, and behavioral measures of nicotine craving as dependent variables. In the studies of the serotonergic system, high ES subjects showed a blunted cortisol response in both studies and high DIS subjects demonstrated a blunted PRL response in study 2. A frequently observed side effect of serotonergic agonists, increase in emotional arousal, was not observable with ipsapirone in high ES and high DIS subjects as compared to low scorers. Behavioral aggression, which had been experimentally induced in study 2, was increased in high ES as well as in high DIS by the 5-HT1a agonist which exerted antiaggressive effects in low scorers. These findings were found compatible with the idea of a generally low responsivity of the serotonergic system in high ES as well as in high DIS types of sensation seekers of 5-HT1a subsensitivity in high DIS and subsensitivity of other postsynaptic 5-HT receptors in high ES. There was no association between SS subscales and DA-induced decrease of PRL, but high ES subjects seemed to tolerate nicotine deprivation better than low ES subjects indicating that they were less susceptible to deprivation of nicotine-induced DA. But craving for nicotine was increased in high ES subjects by the DA agonist lisuride as opposed to the antagonist, which was taken as evidence that DA stimulation may induce approach behavior in high ES. Although only two subscales had been selected for the investigation, this approach suggests both common and different relationships between SS subscales and neurotransmitter systems.

Adult↗
PubMed1996

Influence of severity of chronic inflammatory joint disease on the pharmacokinetics of indomethacin and etodolac.

The goal of this study was to look for correlations between the severity of chronic inflammatory joint disease and pharmacokinetic parameters of nonsteroidal antiinflammatory drugs. Disease severity data (pain severity and magnitude of abnormalities in laboratory tests for inflammation) and pharmacokinetic data (area under the curve in the morning (AUCm) and maximum plasma concentration (Cmax) were collected during a prospective, randomized, double-blind, parallel-group study. Two groups of nine and 11 patients, respectively, were given 300 mg etodolac b.i.d or 50 mg indomethacin b.i.d. by the oral route, for three days, after a 36-hour placebo washout. Univariate analyses demonstrated statistically significant negative correlations between pharmacokinetic parameters of both study drugs and a number of disease severity parameters. In the multivariate analysis of data for etodolac, the sigma erythrocyte sedimentation rate contributed significantly to variations in all pharmacokinetic parameters and explained 100% of the variations in free S-enantiomer AUCm and in total and free S-enantiomer Cmax. For indomethacin, pain contributed to variations in Cmax values of the total and free forms; the sigma erythrocyte sedimentation rate was also a factor in variations in total indomethacin. These negative correlations suggest that severity of chronic inflammatory joint disease may influence the pharmacokinetics of nonsteroidal antiinflammatory drugs.

Administration, Oral↗
PubMed1996

Stereoselective irreversible binding of ketoprofen glucuronides to albumin. Characterization of the site and the mechanism.

We have previously shown that the acyl glucuronide of racemic ketoprofen can irreversibly bind in vitro to plasma proteins (Dubois, N., et ai., Drug Metab. Dispos. 21, 617-623, 1993), but the mechanism of the reaction has not been characterized. In the present study, the reactivity toward albumin of the glucuronide of both ketoprofen enantiomers was investigated. The extent of binding increased with the concentration of both protein and glucuronide. However, the two diastereoisomers showed different reactivities toward human serum albumin (HSA): the maximum yield of adducts with the glucuronide of the S-enantiomer was twice that obtained with the glucuronide of its antipode. The maximum extent of irreversible binding was at 4 hr for the R-ketoprofen conjugate, but was later for the S-form. Chemical modifications of albumin indicated that the glucuronide of the S-isomer reacted only with lysine residues, whereas the R-form linked covalently mainly with tyrosine residues and secondarily with lysine residues. A competition study using specific binding probes and fatty acids showed that the conjugates of S- and R-ketoprofen reacted with amino acids located in sites I and II of HSA, respectively. Taken together, these findings suggest that the irreversible binding of ketoprofen to albumin depends on the stereochemistry of the aglycon: the R-enantiomer binds to site II of the protein probably by a nucleophilic attack by tyrosine and/or lysine residues, whereas adduct formation via the conjugate of the S-enantiomer could occur at site I of HSA by the Schiff base mechanism. This irreversible binding at sites I and II may affect the major function of albumin (i.e. the transport of drugs and endogenous compounds).

Animals↗
PubMed1995

Genetic analysis of the folded structure of yeast mitochondrial cytochrome b by selection of intragenic second-site revertants.

The mutations C133-->Y133, L282-->F282 and G340-->E340 in yeast mitochondrial cytochrome b each lead to a dysfunction of the cytochrome bc1 complex and, consequently, to the absence of growth on non-fermentable substrates. We isolated and characterized, from these mutants, fourteen different intragenic pseudo-revertants of various respiratory sufficient phenotypes. Both first-site and second-site suppressor mutations were found. A novel type of suppressor mutation consisted of the three-base-pair deletion of the parental mutated codon (E340 delta). The results provide, for the first time, evidence for the transmembrane disposition of helices F and G of the current eight-helix cytochrome b model. These two helices are presumably in contact with helix C in the folded protein. A simple modelisation study suggests that the packing of helices C, F and G in cytochrome b may be similar to that of helices I, II and VII in bacteriorhodopsin, respectively. We observed from the study of second-site revertants that compensation across the membrane never occurs. For each revertant, the suppressor mutation and the corresponding target mutation are on the same side of the membrane. This membrane sidedness strengthens the topological constraints imposed by the Q-cycle, namely the necessity of spatial separation of two catalytic reaction sites for ubiquinone.

Amino Acid Sequence↗
PubMed1995

[Inducible cyclooxygenase. New relationships between non-steroidal anti-inflammatory agents and inhibition of synthesis of prostaglandins].

After a brief history of the main discoveries concerning the research on arachidonic acid and its biologically active derivatives, recent findings related to the identification of 2 isoenzymes of the prostaglandin-H synthase (PGHS) are reviewed. These isoenzymes play different roles within the body, since PGHS-1 is involved in homeostasis when PGHS-2 is mainly expressed during the inflammatory reaction. Non-steroidal anti-inflammatory drugs classically inhibit the biosynthesis of prostaglandins but this inhibitory effect depends on the considered isoenzyme. This discovery may have pharmacological and clinical impact but, at the present time, research is focused more on new pharmacological targets than on improving drug prescription.

Adrenal Cortex Hormones↗