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Biomedical subjects

P Netter

Publications and source records attributed to P Netter.

At least 181 records · Page 10Linked to original sources
PubMed1993

Dialysis-associated arthropathy: secondary ion mass spectrometry evidence of aluminum silicate in beta 2-microglobulin amyloid synovial tissue and articular cartilage.

The role of aluminum accumulation in articular tissues of patients affected by dialysis-associated arthropathy (DAA) is questioned. The aim of this work is to identify the nature of these aluminum accumulations by the use of secondary ion mass spectrometry (SIMS). Al/Si ratios of about 1, measured by SIMS, strongly suggest for the first time the presence of aluminum silicates and possibly aluminum hydroxides in amyloid synovial tissue and articular cartilage of 1 patient with DAA and aluminum intoxication. This is thermodynamically consistent with the total dissolved Al and Si contents and pH measured in the synovial fluids. These results are similar to the abnormal Al distribution recently found by SIMS in the forebrain of chronic renal dialysis patients and to the amorphous aluminum silicates identified in the core of senile plaques in Alzheimer's disease.

Aluminum Silicates↗
PubMed1993

Protein binding and stereoselectivity of nonsteroidal anti-inflammatory drugs.

Stereoselective binding of nonsteroidal anti-inflammatory drugs (NSAIDs) can be studied using various techniques. Thus the results obtained by different investigators may be poorly consistent and even contradictory. NSAIDs are bound stereoselectively to serum albumin to different degrees depending on the drug investigated (ibuprofen, indoprofen, carprofen, etodolac, ketoprofen and flurbiprofen). For other drugs, both enantiomers are bound to a similar extent (pirprofen, fenoprofen). This stereoselectivity could vary with experimental conditions, in particular with protein concentration (ketoprofen, etodolac), leading to individual differences. Finally, the stereoselectivity of protein binding and of pharmacokinetics can be compared: differences in binding between enantiomers can explain their differences in pharmacokinetics, once metabolic properties such as inversion have been taken into account.

Animals↗
PubMed1993

Pharmacokinetics and pharmacodynamics of non steroidal anti-inflammatory drugs in synovial fluid.

Since the joint is the target organ of non steroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases, the concentration in the synovial fluid (SF) is an important determinant of clinical response to these agents. Present data indicate that in the SF pharmacokinetic behaviour of NSAIDs depends on their plasma elimination half-life. Moreover, some chiral drugs exhibit stereoselective distribution properties. Finally, pharmacodynamic investigations suggest that inhibition of prostaglandin synthesis in the synovial compartment is the dominant mechanism of action for most, if not all, NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Interleukin-1 beta differentially represses drug-metabolizing enzymes in arthritic female rats.

Experimental arthritis and inflammation have been reported to reduce liver cytochrome P-450-dependent mono-oxygenase activities with subsequent impairment of drug metabolism. Interleukin-1 beta (IL-1) is among the proven mediators of both inflammation and P-450 decrease, although some paradoxical effects were sometimes reported in experimental models of arthritis. The aim of the present study was to evaluate the main liver drug-metabolizing isoenzymes during established collagen-induced arthritis in rats, and to investigate whether a systemic IL-1 treatment was able to mimic or sometimes to reverse the influence of the inflammatory process on these enzymes. Arthritis was induced on day 0 by type II collagen and a low dose (0.2 mg) of N-acetylmuramyl-L-alanyl-D-isoglutamine, and human recombinant IL-1 was administered s.c. at the daily dose of 0.02, 0.2 or 2.0 micrograms per arthritic rat, from day 21 to 25 and on day 28. Ethoxyresorufin-O-deethylation was depressed 6-fold in arthritic rat liver microsomes and the highest dosage of IL-1 potentiated this depression. Pentoxyresorufin-O-deethylation decreased by 50% in arthritic rat, a dose-dependent decrease being observed after IL-1 treatment. Progesterone 6 beta-hydroxylation and P-450 IIIA protein increased by 2-fold in both untreated arthritic rat liver microsomes and those treated by the lowest dose of IL-1. The two higher doses decreased this activity, vs. the dose, to reach the naive level. Lauric acid hydroxylation increased 2-fold in arthritic rat and was further potentiated by IL-1. UDP glucuronosyl transferase IA2 activity was increased 2-fold in arthritic rats, with subsequent decrease after 2.0 micrograms of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Stereoselective binding of etodolac to human serum albumin.

The protein binding of etodolac enantiomers was studied in vitro by equilibrium dialysis in human serum albumin (HSA) of various concentrations varying from 1 to 40 g/liter, by addition of each enantiomer at increasing concentrations. In the 1 g/liter solution, at the lowest drug levels, the (R)-form is more bound than its antipode, the contrary being observed at the highest drug levels. For higher albumin concentrations, S was bound in a larger extent than R. Using the displacement of specific markers of HSA sites I and II, studied by spectrofluorimetry, it was suggested that R and S are both bound to site I, while only S is strongly bound to site II.

Anti-Inflammatory Agents, Non-Steroidal↗
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↗