(1/21) Antinative DNA antibodies as a reaction to pyrazole drugs.
A case history is presented of the occurrence of a high binding capacity for native DNA in the serum of a patient on phenylbutazone. This reverted to normal on stopping the drug. The patient also had a reversible neutropenia and leucopenia, and it is suggested that the high anti-DNA binding capacity was a feature of a drug-induced lupus-like phenomenon. (+info)
(2/21) Oxyphenbutazone-induced goitre.
A woman who had taken oxyphenbutazone for 4 years because of back pain presented with goitre and hypothyroidism. This was shown to be due to an organification defect, caused or aggravated by oxyphenbutazone. (+info)
(3/21) Ligand binding at membrane mimetic interfaces. Human serum albumin in reverse micelles.
The behaviour of human serum albumin in the presence of three chemically distinct ligands: oxyphenylbutazone, dansylsarcosine and hemin, has been compared in buffer and in reverse micelles of isooctane, water, and either sodium bis(2-ethylhexyl)sulfosuccinate or hexadecyl trimethylammonium bromide, systems selected to mimic the membrane-water interface. Upon micellar incorporation, the dansylsarcosine-albumin complex dissociated, as evidenced by fluorescence emission spectroscopy (red shift from 485 nm to 570 nm) and by fluorescence polarization measurements. In contrast, the hemin-albumin complex remained stable in reverse micelles, as judged from the Soret absorption band at 408 nm and the molar absorption coefficient of 8.4 x 10(4) M-1 cm-1. The oxyphenylbutazone to albumin binding curves reveal that while the association constant remained unchanged (Ka approximately 1.0 x 10(5) M-1), only a fraction of the albumin molecules present reacted with the ligand. The results were unaffected by the nature and the concentration of the surfactant. These findings can be interpreted in the light of conformational changes induced in human serum albumin by the large micellar inner surface area. The blue shift of the fluorescence emission maximum from 344 nm in buffer to 327 nm in sodium bis(2-ethylhexyl)sulfosuccinate micelles and the lesser reactivity/accessibility of the fluorophore to oxidation by N-bromosuccinimide, indicate perturbations of the sole tryptophan-214 microenvironment. However, the distance between the indole residue and tyrosine-411 does not seem substantially modified by the 15% decrease affecting the alpha helices of the albumin molecule. It is proposed that the results reported herein reflect the interactions of albumin with a membrane-like interface which generates two protein subpopulations differing in their membrane-surface and ligand affinities. Overall and local conformational changes, originating from this surface-induced effect, may thus constitute a ligand-release facilitating mechanism acting at cellular membrane levels. (+info)
(4/21) Intrinsic mineralocorticoid agonist activity of some nonsteroidal anti-inflammatory drugs. A postulated mechanism for sodium retention.
Because some nonsteroidal anti-inflammatory drugs (NSAID) induce salt and water retention and exhibit other steroid-like actions, studies were performed to ascertain whether these drugs possess intrinsic mineralocorticoid agonist activity. In vitro competitive binding assays utilizing tissue from adrenalectomized rats demonstrated that some NSAID can displace [3H]-aldosterone from renal cytoplasmic mineralocorticoid receptors. Displacement potency for these sites was in the sequence: aldosterone greater than spironolactone greater than phenylbutazone (PBZ) greater than aspirin (ASA) greater than indomethacin (IDM). Concentration ratios required to obtain significant displacement of [3H]aldosterone were high but clearly within the therapeutic range for PBZ and ASA but not IDM. The analogues oxyphenbutazone (OBZ) and sodium salicylate (SS) were similar in binding activity to PBZ and ASA, respectively. Lineweaver-Burk analysis revealed that the inhibition of [3H]aldosterone binding was competitive in nature. In addition, PBZ was shown to prevent the nuclear binding of [3H]aldosterone. In vivo injection of PBZ and ASA resulted in competition for [3H]aldosterone renal binding comparable to the in vitro studies. Administration of PBZ and OBZ to adrenalectomized rats resulted in significant salt retention whereas ASA and SS did not differ significantly from controls. Salt retention elicited by PBZ and OBZ was inhibited by spironolactone, a competitive mineralocorticoid antagonist. These data suggest that, despite nonsteroidal structures, PBZ and OBZ induce salt retention via a receptor-mediated mineralocorticoid pathway analogous to aldosterone action. (+info)
(5/21) Screening, quantification, and confirmation of phenylbutazone and oxyphenbutazone in equine plasma by liquid chromatography-tandem mass spectrometry.
A sensitive liquid chromatographic-tandem mass spectrometric method was developed and validated for screening, quantification, and confirmation of phenylbutazone and oxyphenbutazone in equine plasma. Analytes were recovered from plasma by liquid-liquid extraction followed by separation in a reversed-phase column and identification by mass spectrometry with selected reaction monitoring in negative electrospray ionization mode. Extraction recovery for both analytes was >80%. Limits of detection, quantification, and confirmation for both analytes were 0.01 microg/mL (S/N>or= 3), 0.05 microg/mL, and 0.05 microg/mL, respectively. The assay with d9-labeled phenylbutazone as internal standard (IS) was linear over a range of 0.05-20 microg/mL (r2>0.995). Intra- and interday precision in terms of coefficient of variation was less than 15%. Intra- and interday accuracy (bias%) was within 80-120%. Hemolysis of red blood cells decreased analyte signal intensity but did not affect quantification results because an isotope-labeled IS was used. Analytes were stable in plasma for 24 h at room temperature, 9 days at 4 degrees C, and 45 days at -20 degrees C and -70 degrees C. The method was successfully used in screening, quantification, and confirmation of phenylbutazone in post-competition plasma samples obtained from racehorses. The method is simple, rapid, and reliably reproducible. (+info)
(6/21) Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials.
(7/21) Pharmacokinetics of phenylbutazone and oxyphenabutazone in the pig.
The kinetics of phenylbutazone (pbz) and its main metabolite oxyphenbutazone (oxpbz) were investigated in seven pigs in order to determine if this animal might serve as a model for human investigations. The study was performed in two stages, one as single dose experiments using intravenous injection, the second as infusion experiments. The rate of elimination for both compounds was demonstrated to be much faster than in man. Similar results have been observed in several other animal species. The degree of protein binding (pbz 98%, ox-pbz 97%), the apparent specific volume of distribution (pbz 0.18 1/kg, ox-pbz 0.28 1/kg) and the renal clearance were found to be similar to results obtained in man and rat. Ox-pbz had a higher renal clearance (0.13 ml/min/kg) than pbz (0.003 ml/min/kg) but still the renal excretion constituted only a small fraction of the total elimination (pbz 0.5%, ox-pbz 5%). Provided real steady state conditions were obtained during the infusion experiments calculations based on the results from the single dose experiments in the same animal revealed that between 20 and 60% of the injected pbz was metabolized to the ring-hydroxylation product (ox-pbz). It is concluded that the pig model is not superior to other animal models for studies of pbz/ox-pbz. The rapid elimination pattern is the main problem in relation to human investigations. (+info)
(8/21) Cold injuries in Kashmir, December 1971.
A total of 847 cases of cold injury occurred within the short space of 2 weeks during the Indo-Pakistan conflict in Kashmir in December 1971. The management of these cases and their end results are described. A combination of drugs consisting of low-molecular-weight dextran, an anti-inflammatory agent, and a vasodilator was tried with encouraging results. A conservative attitude towards ablation of necrosed tissues paid good dividends. (+info)