Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The solvent evaporation process has been used to form hydrocortisone-loaded microspheres from poly((+/-)-lactide) (PLA) and a lactide-glycolide copolymer (65/35). Methylene chloride was the casting solvent. Partially hydrolysed (88%) poly(vinyl alcohol) and methylcellulose were used as aqueous phase emulsifiers. Methylcellulose was preferred, because it gave stable emulsions as the amount of hydrocortisone being encapsulated increased whereas poly(vinyl alcohol) did not. With methylcellulose as the emulsifier, a broad size range of spherical microspheres containing up to 50% (w/w) hydrocortisone could be prepared. Thermal and X-ray analyses established that poly((+/-)-lactide) microspheres containing hydrocortisone retained thermal events characteristic of both materials. This is evidence that such microspheres contain, to some extent, crystalline hydrocortisone domains dispersed in a PLA matrix. But most of the encapsulated drug was molecularly dispersed in the PLA glass. The stability of hydrocortisone in microspheres was evaluated in different storage conditions: no degradation of drug was found. The release of hydrocortisone from 250-350 microns diameter microspheres into agitated 37 degrees C water (nitrogen atmosphere) was determined by HPLC analysis. The microspheres evaluated had initial hydrocortisone payloads of 12 to 47% (w/w). The rate of drug release increased as the initial drug payload carried by the microspheres increased. The release data are not adequately described by zero order, first order, or square-root-of-time release kinetics. Drug release from microspheres that contain 12% (w/w) hydrocortisone approached a plateau value well below the amount of drug actually carried by the microspheres. This is particularly true for hydrocortisone encapsulated in lactide-glycolide polymer.
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PMID:The formation and characterization of hydrocortisone-loaded poly((+/-)-lactide) microspheres. 287 87

Noradrenaline (NA) plasma levels were examined in 18 healthy volunteers on 2 consecutive days after a single treatment with either lormetazepam (0.06 mg/kg) (LMZ group), flunitrazepam (0.03 mg/kg) (FNZ group) or placebo (PLA group) in combination with the benzodiazepine (BZ) antagonist Ro 15-1788 (0.1 mg/kg). Behavioural responses (mood changes, anxiety) were also investigated in parallel. Both BZ decreased NA plasma levels to 50% of the basal values 10 min after the injection; administration of Ro 15-1788 15 min later reinstated NA plasma levels to basal values. A second administration of Ro 15-1788 (0.1 mg/kg) 24 h after BZ or PLA treatment increased NA plasma levels, estimated 10 min after the injection in both the LMZ- and the FNZ groups, but not in the PLA group. Behavioural responses measured under the same treatment also indicated minor anxiety responses followed by mood impairment. These data suggest that a stressful situation may be precipitated by the antagonist Ro 15-1788 24 h after a single BZ treatment, which resembles a withdrawal response, and increases NA plasma levels.
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PMID:Changes in noradrenaline plasma levels and behavioural responses induced by benzodiazepine agonists with the benzodiazepine antagonist Ro 15-1788. 287 61

CHAG, that is, porous hydroxyapatite hydrothermally converted from the calcium carbonate exoskeleton of a coral (genus Goniopora), has been shown to be effective as a scaffold for bone ingrowth. The large pores in the material, however, resulted in low compressive strengths. Compressive testing was performed to assess the changes in mechanical properties by coating the internal surfaces of CHAG with DL-PLA. Plugs of CHAG with thick (3:1 chloroform to DL-PLA by weight), medium (10:1), and thin (30:1) coatings as well as uncoated CHAG were then implanted transcortically in the proximal third of the diaphysis of rabbit tibiae to assess the in vivo response. The mechanical tests demonstrated significantly improved compressive strength, stiffness, and energy absorption for coated specimens compared with uncoated specimens. Coated specimens were not significantly different from canine tibial cancellous bone in strength and stiffness although they achieved only 36% of the energy absorption capacity. Specimens from rabbit tibiae were harvested at 3, 12, and 24 weeks for interface shear strength determination and contralaterally for histological and histomorphometric assessment. At 12 weeks, uncoated CHAG plugs developed an average ultimate interface shear stress of 26.7 MPa compared with 17 MPa for specimens with 30:1 coatings and 8 MPa for specimens with 10:1 and 3:1 coatings. At 24 weeks, there were no significant differences in shear stress between any of the specimens. Histomorphometric assessments showed that the ratio of area fraction of new bone to area fraction of new bone and void space increased from 68-70% for specimens with 3:1 and 10:1 coatings at 3 weeks to 85.5-89.5% at 24 weeks. In comparison, uncoated and 30:1 specimens had area fraction ratios of about 82% at 3 weeks and 93% at 24 weeks. Histologic sections demonstrated direct apposition of new bone to both the coating and the hydroxyapatite as well as degradation of the coating.
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PMID:Mechanical and bone ingrowth properties of a polymer-coated, porous, synthetic, coralline hydroxyapatite bone-graft material. 289 22

LG 30435 (N-methylmequitazine) was assayed in passive lung (PLA) and cutaneous (PCA) anaphylaxis in guinea-pigs and rats. At doses from 0.3 to 3 mumol kg-1 i.v., it produced a dose-dependent inhibition of guinea-pig PLA and of rat PCA and PLA, while the parent compound was ineffective or poorly effective up to 3 mumol kg-1. An attempt was made to elucidate the mechanism of LG 30435's action in these anaphylactic models, by means of various antagonists. It was tentatively concluded that different mechanisms are involved in the protective action of LG 30435 in each of the three models: histamine antagonism, possibly accompanied by an inhibition of the effects of peptido-leukotrienes in guinea-pig PLA; histamine antagonism in rat PCA and 5-hydroxytryptamine antagonism in rat PLA, possibly accompanied by a mast-cell stabilizing action in both cases. LG 30435 is devoid of smooth muscle relaxant effects on the airways and its demonstrated anticholinergic and anti-PAF effects do not appear to be involved in its antiallergic action.
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PMID:Mechanisms of the antiallergic action of N-methylmequitazine (LG 30435). 290 Mar 3

Ro 15-1788, a selective benzodiazepine (BZD) antagonist, is known to precipitate withdrawal reactions in BZD-pretreated animals. We examined whether a high dose of Ro 15-1788 can precipitate withdrawal reactions relating to behavior and changes in the stress-hormone plasma levels after acute BZD treatment in man. On two consecutive days, 15 min and 24 h respectively after a single treatment with either lormetazepam (0.06 mg/kg: LMZ group), flunitrazepam (0.03 mg/kg: FNZ group) or placebo (PLA group), 18 healthy volunteers received two injections of Ro 15-1788 (0.01 mg/kg). Behavioral responses (mood changes, anxiety), cortisol and prolactin plasma levels, and physiological parameters were examined. In all groups there were only slight changes in the circulation parameters. Minor anxiety reactions were seen after Ro 15-1788, which occurred the 1st day in the PLA group and the 2nd day in the BZD groups. Depression was noted especially in the FNZ group after both injections of Ro 15-1788. The physiological morning decrease in cortisol plasma level was influenced on the 1st day in the LMZ group (2 volunteers showed high plasma levels) and the 2nd day in the FNZ group: a slight increase of cortisol plasma level was measured after the 2nd injection of Ro 15-1788. Prolactin plasma levels arose immediately after LMZ injection and continued to increase after Ro 15-1788 injection. No increase in prolactin plasma levels was found in the other groups or in the LMZ group after the 2nd challenge by Ro 15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Benzodiazepine antagonism by RO 15-1788: psychometric, hormonal and biophysical parameters]. 290 13

Serum from 48 patients with acute pancreatitis (21 with interstitial-edematous and 27 with necrotizing pancreatitis) was monitored for immunoreactive (IR) phospholipase A2 (PLA2) protein concentration and PLA catalytic activity. In both groups within 48 h after start of acute pancreatitis an up to tenfold increase of IR-PLA2 was demonstrable. Determination of IR-PLA2 revealed no differences between the groups. In contrast, determination of PLA catalytic activity allowed us to differentiate between patients with interstitial-edematous and necrotizing pancreatitis.
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PMID:Prognostic value of serum phospholipase A in acute pancreatitis. 292 55

Inflammatory cells, e.g., neutrophils, monocytes, and macrophages are presumed to be a source of circulating phospholipase A in nonpancreatic diseases. Therefore, we investigated in a preliminary study whether serum phospholipase A activity is related to leukocyte counts in 43 patients with hematological diseases. Serum PLA activity was significantly increased in patients with Hodgkin's disease, acute monocytic leukemia, myelofibrosis with myeloid metaplasia, and polycythemia vera when compared with patients with chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute myelogenous leukemia, but did not correlate with total leukocyte counts.
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PMID:Serum phospholipase A in hematological diseases. 292 59

Pokeweed-mitogen-induced IgG secretion, Con A suppression and T cell surface markers were measured in 30 chronic progressive multiple sclerosis (MS) patients and 21 healthy controls. Mean IgG secretion was higher in the MS patients than in the controls (2392 +/- 270 vs 1499 +/- 243); Con A suppression was lower (4 +/- 5% vs 24 +/- 4%) and the CD4/CD8 ratio was higher (4.1 +/- 0.4 vs 2.9 +/- 0.4). The above assays were used in vitro to monitor the effects of Wellferon (lymphoblastoid interferon) injections on this group of MS patients. Before treatment the INF-group (n = 14) did not differ from the PLA-group (n = 16). After 1 week of daily injections the level of IgG secreted was dramatically reduced in the INF group (629 +/- 96 ng/ml) compared to the PLA-group (1756 +/- 319 ng/ml). There was no change in either Con A suppression or T cell surface markers. IgG secretion remained lower in the INF-group for the 6 month treatment period. Following cessation of the injections and a 6 month washout period, IgG secretion in the INF-group rose and was equivalent to that observed in the PLA-group. A series of lymphocyte subset mixing experiments implicates the B lymphocyte subset as being directly affected by interferon injections in vitro.
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PMID:Reduction of immunoglobulin G secretion in vitro following long term lymphoblastoid interferon (Wellferon) treatment in multiple sclerosis patients. 295 31

36 patients with 68 aorto-coronary venous bypass grafts (45 of which were angiographically patent) were examined via DSA (DV12V, serial mode, Philips) and angiography. Imaging was triggered via R waves, and effected in RAO 30 degrees, LAO 60 degrees, and AP projection. 63 of the 68 grafts were correctly detected (92.7%). Two anterior interventricular branch grafts (RIVA = ramus interventricularis anterior) were not visualised via DSA (95.6% sensitivity). One graft each to the RIVA, to the right coronary artery (RCA), and to the posterior branch of the lateral cutaneous branches of intercostal arteries (PLA), were falsely found to be patent (87% specificity). Grafts were visualised in full length. In some cases morphological changes of the walls were also visible.
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PMID:[Peripheral venous digital subtraction angiography in the follow-up of aortocoronary venous bypass grafts]. 298 88

We analyse recent ESR measurements on Ca2+ ATPase and Myelin proteolipid apoprotein reconstituted in phosphatidylcholine bilayer membranes. Our intention is to discover whether the measurements indicate significant protein-protein repulsive or attractive interactions. In order to do so we have studied a model of a lipid bilayer membrane containing transbilayer proteins. It represents the proteins by hexagons moving on a triangular lattice interacting via an energy E0 which can be attractive, repulsive or zero. The last-named represents that all of the Ca2+ ATPase data is best described either by the "random" model or, possibly, by one in which there is a small repulsive interaction, but not by the "annulus" model or one in which there is always at least one layer of lipid chains between every pair of proteins. We find that all of the Myelin PLA data is best described by a "random" distribution of hexamers and not by an "annulus" model of hexamers. We suggest measurements that can be done in order to unambiguously settle the question of whether these systems are best described by a "random"-type model or an "annulus"-type model.
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PMID:Protein lateral distribution in lipid bilayer membranes. Applications to ESR studies. 299 20


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