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Biomedical subjects

P Netter

Publications and source records attributed to P Netter.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

The antagonism of ipsapirone induced biobehavioral responses by +/- pindolol in high and low impulsives.

The present study was conducted to investigate whether +/- pindolol antagonizes ipsapirone induced biobehavioral changes in a personality dependent way. Our previous work demonstrated that high impulsives show higher immune cell responses than low impulsive subjects upon treatment with ipsapirone. A total number of 80 healthy male volunteers received placebo (N = 20) or 10 mg ipsapirone (N = 20), 30 mg +/- pindolol (N = 20), or a combination of 30 mg +/- pindolol and 10 mg ipsapirone (N = 20). Each group consisted of 10 low and 10 high impulsive subjects. Since 5-HT related drugs induce thermoregulatory responses, the study took place in a climate chamber with a constant ambient temperature. Blood samples (for measurement of CD4+ cell counts) were drawn from an indwelling catheter invisibly for the subjects. The results clearly demonstrate that the ipsapirone induced decreases in body temperature and number of peripheral CD4+ cells are more pronounced in high impulsives. +/- Pindolol antagonizes thermoregulatory and CD4+ cell responses. The results are discussed with respect to mechanisms of alteration in 5-HT function related to impulsivity.

Adrenergic beta-Antagonists↗
PubMed1997

[Explanatory models of anxiety from the viewpoint of biopsychology and pharmacopsychology].

To understand the biological basis of anxiety, the following psychological aspects are discussed: The difference between "trait" and "state" anxiety, types of anxiety as related to knowledge about causes and consequences, anxiety as a chronological process involving coping strategies and different levels of responses. The lack of specificity is physiological indicators of anxiety is demonstrated by experiments based on electrodermal and cardiovascular responses. Among hormones, special emphasis is placed on the constellation between catecholamines and cortisol as being relevant for anxiety research. It is emphasized that configurations of hormone parameters may be more relevant predictors for anxiety than single response values, and the study of postoperative catecholamine and cortisol responses is used for demonstrating differences between patients in a high and low preoperative state of anxiety. Differences are observed only on the emotional and pain response levels, but not in physiological parameters. The neurophysiological model representing central nervous system substrates for anxiety is the behavioural inhibitory system described in the theory by Gray [17], and the most relevant transmitters noradrenaline, serotonin, and the GABA-system are discussed with regard to their relevance for anxiety in animal studies, in studies using provocation tests with pharmacological substances, and in clinical studies with anti-anxiety drugs. Experimental anxiety research in psychology is frequently characterised by significant interactions between many mediators of responses, in particular the type of stressor, the level of trait anxiety and other personality variables, and the type of substances used. It is concluded that stressors as well as drugs frequently do not specifically induce anxiety but may nonspecifically affect general arousal and may only be operating in certain groups and certain levels of stress intensity.

Anxiety↗
PubMed1997

A comparative study of duplications in bacteria and eukaryotes: the importance of telomeres.

The genomes of three bacteria (Haemophilus influenzae, Mycoplasma genitalium, and Escherichia coli) and two eukaryotes (Saccharomyces cerevisiae and Caenorhabditis elegans) were compared. The distribution of their putative open reading frames (ORFs) was studied, and several conclusions were drawn: (1) All of these genomes, even the smallest, exhibit a significant proportion (7%-30%) of duplicated ORFs. This proportion is a function of genome size and appears unrelated to the bacteria/eukaryote division. (2) Some of these ORFs constitute families of up 20 or more members. (3) The levels of sequence similarity within these families are highly variable and their distribution is different among bacteria and eukaryotes. (4) In yeast, there are topological relationships between members of the same family. The paired ORFs are frequently in the same orientation with regard to their respective telomeres and located at comparable distances from them.

Animals↗
PubMed1997

Relations between functional, inflammatory, and degenerative parameters during adjuvant arthritis in rats.

We assessed the time-course of adjuvant arthritis (AA) in Lewis rats, using biotelemetry to monitor the rat's spontaneous locomotor activity and body temperature, and studied the evolution of the arthritic index, circulating concentrations of inflammation-promoting cytokines, cartilage proteoglycan synthesis, and the effect of indomethacin as a cyclooxygenase inhibitor to evaluate prostaglandin (PG) contribution in AA. The injection of complete Freund's adjuvant on day 0 (D0) induced a marked, transient loss of locomotor activity (D1-D4; initial phase) and then a second phase of hypomobility peaking on D15 and thereafter irreversible (D16-D20; arthritic phase). Fever peaked first on D1 and again between D13 and D17. The primary hyperthermia was associated with increases in plasma interleukin-6 and tumor necrosis factor-alpha concentrations and seemed to be partly PG dependent. Proteoglycan synthesis inhibition in the patellar cartilage increased gradually, spreading from the injected paw to the contralateral paw. It was corrected on D20 by preventive and curative indomethacin treatments. Indomethacin also greatly relieved hypomobility during the systemic phase of AA (D10-D15). The combination of information about cartilage metabolism, body temperature, locomotor activity, and cytokine in this study permits analysis of analgesic, antipyretic, anti-inflammatory, and chondroprotective properties of drugs in the various phases of AA. Thus, using a new methodology, we have discriminated the different phases of the disease and confirmed the symptomatic and systemic inhibitory effect of indomethacin on fever, activity, and cartilage metabolism.

Activity Cycles↗
PubMed1997

Effects of continuous infusion of interleukin 1 beta on corticotropin-releasing hormone (CRH), CRH receptors, proopiomelanocortin gene expression and secretion of corticotropin, beta-endorphin and corticosterone.

A number of recent studies suggest that interleukin 1 beta (IL-1 beta) is a major mediator of hypothalamo-pituitary-adrenal (HPA) responses following infectious aggression. We investigated whether IL-1 beta mediates long-term changes in HPA activity and studied the cellular regulation of the anterior pituitary. To mimic chronically elevated IL-1 beta production thought to occur during infectious diseases, osmotic pumps (Alzet type) were implanted in the peritoneal cavity of male rats and hIL-1 beta was infused continuously at rates of 1 or 3 micrograms/day. Effects of hIL-1 beta action on plasma ACTH, beta-endorphin (beta-EP) and corticosterone (CORT) secretion and on anterior pituitary (AP), ACTH and beta-EP content were followed. In addition, hypothalamic (HT) CRH mRNA and in AP, CRH receptor (CRH-Rc) mRNA, POMC nuclear primary transcript RNA, POMC nuclear intermediate processing RNA and POMC nuclear and cytoplasmic mRNA were quantified using a highly sensitive solution hybridization nuclease protection assay. Continuous infusion of hIL-1 beta stimulated the HPA axis at varying degrees. Increased HT CRH gene expression, AP POMC gene transcription, ACTH and beta-EP release occurred only during the first 3 days of the treatment. A long-lasting enhancement of ACTH and beta-EP synthesis and of POMC gene expression resulted from activated POMC gene transcription followed by an increased POMC mRNA stability and decreased POMC mRNA turnover. In the AP, stimulation of ACTH and beta-EP secretion and POMC gene transcription disappeared after continuous IL-1 beta treatment, possibly in part due to a refractory process mediated by decreased CRH-Rc gene expression in corticotropes.

Adrenocorticotropic Hormone↗
PubMed1997

Assessment of articular cartilage and subchondral bone: subtle and progressive changes in experimental osteoarthritis using 50 MHz echography in vitro.

The main objectives of this work were to demonstrate the potential of 50 MHz echography for assessing initial and progressive morphological and structural changes of articular cartilage and bone developed in an experimental model of osteoarthritis (OA). Degenerative lesions were induced in rat knees by the unilateral intra-articular injection of a 3 mg dose of mono-iodo-acetic acid. To assess the lesion progression, the animals (n = 30) were sacrificed at different time intervals up to 8 weeks after the injection. Three-dimensional echographic data were acquired in vitro on patellar cartilage and bone at various stages of the remodeling process using a scanning ultrasound microscope. Changes involving the OA cartilage characteristics are discussed relative to those of the contralateral control joint which received a placebo. Images of control cartilage showed a smooth hyperechoic articular surface and an echoic matrix. The cartilage thickness was 266 +/- 44 microns (mean +/- SD) in the central region of the tissue. The precision of ultrasonic thickness measurements was better than 1.3%. First changes in cartilage internal structure and subchondral bone appeared on ultrasound images 3 days after the injection and were even more evident by day 7. They resulted in a slight thinning of the cartilage, a 30% increase of its internal structure echogenicity, and the appearance of echoic zones in subchondral bone. Histologic findings confirmed chondrocyte depletion and degeneration, decrease of matrix proteoglycans, and fibrovascular connective tissue proliferation at the subchondral plate. Progressive and severe lesions at both bone and cartilage surface and internal structure were assessed and correlated to histologic features. These results show that high resolution echography is sensitive to subtle and progressive osteochondral remodeling. This technique has the potential to be used for intra-articular quantitative imaging and assessment of early changes in bone and cartilage structure associated with natural human disease.

Animals↗
PubMed1997

Cyclo-oxygenase isoenzymes. How recent findings affect thinking about nonsteroidal anti-inflammatory drugs.

The discovery of at least 2 cyclo-oxygenase (COX) isoenzymes, referred to as COX-1 and COX-2, has updated our knowledge of nonsteroidal anti-inflammatory drugs (NSAIDs). This has lead investigators to reconsider what can be awaited from this class of drugs. The 2 COX isoenzymes share structural and enzymatic similarities, but are specifically regulated at the molecular level and may be distinguished apart in their functions, although some physiological overlap between them does occur. The major goal in developing selective COX inhibitors is to improve NSAID tolerability. Classic NSAIDs preferentially inhibit COX-1 in vitro, but it appears hazardous to judge their gastrointestinal (GI) safety profile from these data. New compounds with a high selectivity for COX-2, especially those that are non-acidic, may be better tolerated in the GI tract. While these compounds also might have a potential use in various diseases such as colorectal cancer and neurodegenerative diseases of the Alzheimer type, the possible appearance of adverse effects, perhaps renally-related, must be taken into consideration. Finally, well-designed large clinical trials are required to adequately estimate both the promising therapeutic advantages that may be offered by highly selective NSAIDs, and the potential drawbacks that may be inherent with prolonged COX-2 inhibition.

Animals↗
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↗