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Biomedical subjects

P Netter

Publications and source records attributed to P Netter.

At least 163 records · Page 9Linked to original sources
PubMed1992

Regulation of the maize HRGP gene expression by ethylene and wounding. mRNA accumulation and qualitative expression analysis of the promoter by microprojectile bombardment.

The expression of the maize gene coding for a hydroxyproline-rich glycoprotein (HRGP) has been studied by measuring the mRNA accumulation after wounding or ethylene treatment. RNA blot and in situ hybridization techniques have been used. The temporal and tissue-specific expression has been observed: the cells related to the vascular system show the more intense HRGP mRNA accumulation. Transcriptional constructions of the maize HRGP promoter have been tested on different maize tissues by microbombarding. A 582 bp promoter is able to direct the expression of the gus gene on calli and young leaves. Constructions having shorter promoter sequences lose this ability. The 582 bp construction retains the general specificity of expression observed for the HRGP gene.

Ethylenes↗
PubMed1992

The unusual reversion properties of a mitochondrial mutation in the structural gene of subunit I of cytochrome oxidase of Saccharomyces cerevisiae reveal a probable histidine ligand of the redox center.

We have analyzed a mutation in the mitochondrial gene oxi3 coding for subunit I of cytochrome-oxidase in the yeast Saccharomyces cerevisiae. This mutation replaces one of the seven invariant histidines of the polypeptide (position 378) by a tyrosine, and leads to a respiratory deficient phenotype. A total of 157 revertants, which have recovered the ability to grow on a respiratory substrate, have been selected from this mutant (tyrosine 378). The nature of the reversion has been analysed by a rapid screening procedure and 32 of the revertants have been sequenced. They are all true back-mutations reintroducing the histidine in position 378. This very exceptional situation suggests that this histidine is a ligand of the redox center of cytochrome oxidase.

Amino Acid Sequence↗
PubMed1992

The pharmacokinetics of tiopronin and its principal metabolite (2-mercaptopropionic acid) after oral administration to healthy volunteers.

We have studied the pharmacokinetics of tiopronin and its principal metabolite, 2-mercaptopropionic acid (2-MPA) in healthy volunteers after the oral administration of 500 mg (2 Acadione tablets), followed by simultaneous assay of the two compounds in plasma over a period of 48 h using a new method (emission of fluorescence after HPLC and post-column derivatization by pyrene-maleimide). The absorption of tiopronin was slow (tmax between 4 and 6 h) and the plasma concentrations subsequently fell biexponentially. The principal metabolite 2-MPA appeared later in the plasma (tmax between 10 and 12 h after a lag-time of 3 h) then disappeared monoexponentially. About 15% of the tiopronin was metabolized to 2-MPA.

Administration, Oral↗
PubMed1992

Effect of age on the disposition of sodium fluoride.

Sodium fluoride (NaF) is used in the treatment of axial osteoporosis and so is mostly given to old patients. Since its pharmacokinetics has not been studied in the elderly, the pharmacokinetics of an enteric-coated tablet containing 50 mg NaF has been investigated in 15 aged inpatients (aged 65 to 75 y) and 12 young healthy volunteers (aged 21 to 26 y). The serum AUC of fluoride was 1.7-time higher in older than in younger subjects. There was a strong inverse correlation between the AUC and either body surface area (BSA) or glomerular filtration rate (GFR), both of which were very much lower in the elderly. This concluded that if efficacy or safety are related to the bioavailability of fluoride, it may be valuable to adjust the dosage of fluoride accordingly to the GFR and BSA.

Adult↗
PubMed1992

Pro- and anti-inflammatory properties of human recombinant IL-1 beta during experimental arthritis in rats: 1. Dependence on dose and severity threshold.

The effects of human recombinant interleukin-1 beta (HrIL-1 beta) were investigated in arthritic rats sensitized with type II collagen (CII) and muramyl dipeptide (MDP). When administered subcutaneously (sc) daily during established arthritis, low (0.02 micrograms) and medium (0.2 micrograms) HrIL-1 beta doses exerted paradoxical beneficial properties on paws with moderate and severe inflammation, respectively. In contrast, the highest dose (2 micrograms) had a pejorative effect on developing arthritis. In addition, HrIL-1 beta attenuated paw volume and deterioration of the joints as assessed radiologically. Hence, paw inflammation response to IL-1 exposure depended on the dosage and the severity of previous arthritis prior to the IL-1 challenge. Some of these paradoxical activities may be due to the capacity of IL-1 to induce its own inhibitors or feedback loops thus counterbalancing its phlogistic properties.

Animals↗
PubMed1992

Dialysis-associated arthropathy: a multicentre survey of 171 patients receiving haemodialysis for over 10 years. The Co-operative Group on Dialysis-associated Arthropathy.

In order to determine the prevalence of dialysis-associated arthropathy (DAA) and what factors favour its development, we conducted a survey in 19 centres in northeastern France, of all patients receiving haemodialysis for over 10 years (171). A diagnosis of DAA was made in 84 patients (49%) by two investigators, using as criteria single or combined presence of carpal tunnel syndrome (32%), erosions and bone cysts of the large limb joints (33%) and destructive spondylarthropathy (14%). The 84 patients with DAA were compared with the 87 dialysis patients free of these clinical or radiological abnormalities. The affected patients were significantly older at the start of dialysis than unaffected patients. The risk of developing carpal tunnel syndrome increased with the duration of dialysis. Amyloid deposits were found in carpal tunnel tissue obtained from 24 of the 39 operated patients (62%) during surgery. Destructive spondylarthropathy was significantly associated with the presence of disc calcifications and more frequent in AN 69-treated patients in whom secondary hyperparathyroidism appeared to be more severe. The use of an AN 69 membrane for at least 90% of the dialysis period (in 15 patients) was not associated with a lower prevalence of DAA. We found that after 10 years of haemodialysis DAA occurred whatever type of membrane was used and the prevalence increased with the patient's age and the duration of dialysis.

Adolescent↗
PubMed1992

Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol.

Since the antipyretic and probably the analgesic effects of paracetamol are, at least in part, centrally mediated, its plasma and cerebrospinal fluid (CSF) concentrations were measured in 43 patients with nerve-root compression pain. Each subject was given a short i.v. infusion of 2 g propacetamol, a prodrug which is hydrolysed to paracetamol within 7 min. Single blood and CSF samples were drawn concomitantly in each patient at intervals between 20 min and 12 h. Maximum CSF drug concentrations were observed at the 4th hour, subsequent concentrations exceeding those in plasma. The elimination half-life of paracetamol calculated from pooled data was shorter in plasma (2.4 h) than in CSF (3.2 h). The time-course of paracetamol in CSF may parallel that of analgesic effect.

Acetaminophen↗
PubMed1992

The in vitro effect of amodiaquine on bone marrow granulocyte-macrophage progenitor cells from normal subjects.

Amodiaquine is used for antimalarial prophylaxis and treatment and has been associated with neutropenia and agranulocytosis in man. The effect of the drug on the in vitro growth of bone marrow human myeloid progenitor cells (GM-CFU) was tested using the soft agar culture technique: 42 haematologically normal subjects were studied and it was found that amodiaquine, at concentrations tested in vitro (0.005, 0.05 and 0.5 micrograms.ml-1), had no quantitative effect on the colony and cluster growth. Our results argue against direct toxicity of the drug on GM-CFU. Therefore, in cases of amodiaquine-associated neutropenia, alternative mechanisms should be considered: a abnormally sensitive GM-CFU; b) toxic effect of metabolites such as desethyl-amodiaquine; c) immune-mediated toxicity.

Adolescent↗
PubMed1992

The in vivo systemic effect of human recombinant interleukin-1 beta on fibronectin in rats.

The in vivo systemic effect of interleukin (IL)-1 beta on plasma and cartilage fibronectin was studied in arthritic rats, as well as alpha 1-acid glycoprotein and albumin. Plasma fibronectin showed a 27% increase in the arthritic group, while alpha 1-acid glycoprotein increased 22-fold and albumin decreased by 46%. IL-1 effect depended on the administered dose. 2 micrograms injection significantly increased plasma fibronectin and alpha 1-acid glycoprotein. In cartilage, fibronectin was significantly modified in arthritic animals but increased in a dose-related manner after IL-1 treatment. As IL-1 increases fibronectin-degrading enzyme production and as some of these fragments can develop properties that do not possess the intact molecule, one can postulate a vicious circle in matrix degradation in the inflammatory process of the joint.

Animals↗
PubMed1991

Protein binding of indomethacin in human cerebrospinal fluid.

The binding of the non-steroidal anti-inflammatory drug indomethacin to proteins in human cerebrospinal fluid (CSF), drawn during lumbar puncture from 10 patients affected by lumbosciatica, was measured by equilibrium dialysis and spectrofluorimetry. Similar binding studies on human serum albumin solutions (0.5 and 1 g/L) were performed using the same techniques. The mean binding percentage of indomethacin determined by equilibrium dialysis was 40%. The results obtained by both techniques allowed us to conclude that the binding of indomethacin in CSF was essentially due to albumin.

Dialysis↗
PubMed1991

[Effects of cyclandelate on the CNS--a double-blind, placebo-controlled study of healthy subjects].

The effect of cyclandelate (Natil) on the CNS was tested in a double-blind, placebo-controlled pilot study on 48 healthy males using a single oral dosage of 1200 mg. The EEG was evaluated quantitatively by spectral analysis before and one hour as well as two and a half hours after drug or placebo administration under resting conditions and while performing a test of mental arithmetic. Under resting conditions the power in the alpha 2 frequency band of the signals from the frontal and central recordings was increased in the cyclandelate group in comparison to the placebo group. This effect was still observed two and a half hours after drug intake. Under the condition of mental arithmetic no drug related effect was observed in the EEG. The cyclandelate induced increase of spectral power in the alpha 2 frequency band under resting conditions demonstrates a general effect of cyclandelate on the CNS. The results are discussed with respect to the known age related decrease of spectral power in the alpha frequency band. The established effect of cyclandelate in young healthy subjects calls for a study with chronic treatment in elderly subjects or patients with cognitive deficits.

Adult↗
PubMed1991

Assay of synovial fluid hyaluronic acid using high-performance liquid chromatography of hyaluronidase digests.

A high-performance liquid chromatographic method for the determination of hyaluronic acid levels in synovial fluids has been developed. The hyaluronidase sample digests, containing an internal standard (benzoic acid), were separated on a reversed-phase octadecylsilyl column eluted with 0.01 M tetrabutylammonium phosphate-acetonitrile (83:17, v/v) at pH 7.35. The determination was made on 1:10 diluted samples, by using a calibration curve from 50 to 500 micrograms/ml of human umbilical cord hyaluronic acid. For validation, the synovial fluids were simultaneously analysed by this method and a radiometric method: a high correlation was found between the two (correlation coefficient 0.94). The proposed method can be used to determine specifically the high hyaluronic acid levels of synovial fluids without interferences from other glycosaminoglycans or non-steroidal anti-inflammatory drug treatment.

Adolescent↗
PubMed1991

Determination of 2-mercaptopropionylglycine and its metabolite, 2-mercaptopropionic acid, in plasma by ion-pair reversed-phase high-performance liquid chromatography with post-column derivatization.

A simple and fast high-performance liquid chromatographic method was developed for the simultaneous measurement of 2-mercaptopropionylglycine (Tiopronine) and its metabolite (2-mercaptopropionic acid) in human plasma after the administration of a pharmaceutical dosage form (Acadione). The sample treatment before high-performance liquid chromatographic analysis consisted of the reduction of the corresponding disulphides by tri-n-butylphosphine and protein precipitation with ethanol. Separation was achieved by ion-pair high-performance liquid chromatography on a reversed-phase column (LiChrospher RP 18e) with cetrimonium bromide as counter ion and detection by fluorimetry after post-column derivatization with a selective thiol reagent, i.e. pyrenemaleimide. The high frequency of the analyzed samples and validation results make the method suitable for pharmacokinetic studies, and this was demonstrated by the first results obtained after the administration of an oral dose of 500 mg of Tiopronine to two healthy subjects.

Chemical Precipitation↗
PubMed1991

Auto-immune spondylodiscitis associated with collagen induced arthritis in rats: high field MRI findings.

The spinal involvement of the tail was studied in Wistar Furth rats immunized with bovine native type II collagen. Focal caudal autoimmune spondylodiscitis occurred 5 weeks after sensitization, as assessed histopathologically. High field Magnetic Resonance Imaging (MRI) was useful in depicting these caudal abnormalities that were related to juxta-diskal enthesitis. The occurrence of such inflammatory enthesopathies could serve as an experimental approach for physiopathological and therapeutical studies of spondylarthropathies.

Animals↗
PubMed1991

Tenoxicam concentrations in synovium and joint cartilage in humans.

Tenoxicam is an NSAID of the oxicam group. Its distribution in articular tissues was investigated in 12 patients who required total arthroplasty of the hip. They were given tenoxicam 20 mg once daily for 8 to 30 days before surgery. Blood, synovium and cartilage samples were taken concurrently during surgery, about 14 hours after the last tenoxicam dose. The tissues were ground using a freeze grinder. Tenoxicam was assayed by HPLC. Tenoxicam concentrations averaged 6.21 +/- 3.81 micrograms/ml in plasma, 7.56 +/- 4.67 micrograms/g in synovium and 2.05 +/- 1.43 micrograms/g in cartilage. The individual synovium/cartilage ratios ranged from 1.9 to 9.7. Finally tenoxicam exhibited more affinity for its target organ (synovial tissue) than for joint cartilage.

Adult↗
PubMed1991

Types of aggressiveness and catecholamine response in essential hypertensives and healthy controls.

Relationships between plasma catecholamine responses, and levels and types of aggression in hyper- and normotensives were investigated by analyses of data obtained in a large psychophysiological experiment on 97 hypertensives (EH) and 98 normotensives (CO) each. Subjects were divided according to levels (high vs low) and types (repressed vs manifest) of aggressiveness according to self rating questionnaire scores. Their plasma catecholamine responses to defined stressors indicating sympathetic arousability were compared by four factor analyses of covariance adjusting for age. Repressed aggression was significantly more frequent among male EH, whereas manifest aggression was significantly more frequent among the male COs. High as compared to low hostility was associated with significantly elevated values of plasma epinephrine in EH but not in CO. The immediate norepinephrine stress response was blunted but showed a delayed increase during the subsequent period of rest in high aggressives of both the EH and CO group, a pattern particularly pronounced in repressed aggressive hypertensives. Neither cardiovascular reactions nor speed of performance were observed to be substantially different in subjects of repressed and of manifest hostility. It was concluded that aggression in general is characterized by a delayed norepinephrine stress response and that an association with high epinephrine is typical for aggressiveness in hypertensives. Repressed hostility, however, does not produce a sympathomedullary pattern substantially different from that of manifest aggression thus casting doubt on the physiological significance of repression claimed by Alexander.

Aggression↗