Operation PAR in St. Petersburg received National Institute on Drug Abuse support in 1989 and state and local appropriations to establish PAR Village, a research demonstration program for treatment of cocaine abusing women with young children. Adjacent to PAR's residential therapeutic community, it includes 14 housing units and a day-care center for infants and children. Women live with their children while receiving long-term residential care. The program is being systematically evaluated by researchers from the University of South Florida Department of Psychiatry and Behavioral Medicine. Retention in treatment and post-discharge outcomes of the women are compared with those involved in the standard program where children remain in the community with relatives or are placed in foster care. Preliminary results suggest the demonstration program increases retention in treatment.

Adolescent↗

PubMed1992

Electrophoresis and silver staining of rat urinary proteins including alpha 2u-globulin (rat n II).

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining have been used to monitor the fractionation of rat urinary proteins by Amicon Centriprep C30/C10 ultrafiltration and to assess the purification of alpha 2u-globulin, a laboratory animal allergen, precipitated by exhaustive dialysis. Factors influencing the protein composition of rat urine have been identified. Dialysis procedures have been evaluated for precipitation of alpha 2u-globulin and ultrafiltration used for further purification of the allergen.

Alpha-Globulins↗

PubMed1992

Patterns of substance use in the medical profession.

National drug use surveys of medical students and resident physicians in 1987 found that medical school was not a time when students began to use drugs, nor was it a time when they engaged in heavy use. Medical students and resident physicians reported lower rates of illicit drug use than their age and gender counterparts. Although males generally were more likely to use substances than females, young male and female physicians resembled one another in their current rates of substance use more than they resembled their gender counterparts in society.

Adult↗

PubMed1992

Determining total protein content of urine: centrifugation results in precipitation of the protein-coomassie brilliant blue dye complex.

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Centrifugation↗

PubMed1991

Drug interference in the Bradford and 2,2'-bicinchoninic acid protein assays.

The interference of a range of drugs and related substances has been investigated in the Bradford Coomassie brilliant blue (CBB) protein dye-binding assay and the 2,2'-bicinchoninic acid (BCA) protein assays. Chlorpromazine was the only substance to interfere in the CBB assay but the interference was slight. In contrast, the BCA reagent interacted strongly with chlorpromazine, the penicillins, vitamin C, and paracetamol and the mode of interference varied with the test substance. The chlorpromazine produced turbidity and an atypical color. The penicillins show a slow but normal color response while vitamin C and paracetamol gave an immediate and intense response.

Drug Interactions↗

PubMed1991

Chiral inversion of 2-arylpropionic acid non-steroidal anti-inflammatory drugs--II. Racemization and hydrolysis of (R)- and (S)-ibuprofen-CoA thioesters.

The inversion of 2-arylpropionic acids (2-APAs) has become the subject of much attention. It is a unique reaction specific to this group of drugs. Inversion proceeds via stereoselective activation of the R-enantiomer to its CoA thioester whereby it is then racemized and hydrolysed to release free drug. The racemization and hydrolysis processes have been examined in this study using chemically synthesized CoA thioesters of the ibuprofen enantiomers and in vitro models employing rat liver homogenate and the mitochondrial and microsomal fractions as the source of the 'racemase' enzymes. Rat liver homogenate mediated the racemization and hydrolysis of both (R)- and (S)-ibuprofen-CoA thioesters. The rat liver mitochondrial fraction similarly mediated racemization and hydrolysis of both CoA thioesters. There was less racemase activity in the rat liver microsomal fraction and the data indicated that this fraction may contain two hydrolases which act separately on the (R)- and (S)-ibuprofen-CoA thioesters. The data are further evidence that the stereoselectivity of the CoA synthetase controls the overall stereoselectivity of inversion.

Animals↗

PubMed1991

Electrophoresis of serum isoenzymes and proteins following acute myocardial infarction.

The clinical significance of the serum enzymes creatine kinase (CK, EC 2.7.3.2), lactate dehydrogenase (LD, EC 1.1.1.27) and aspartate aminotransferase (EC 2.6.1.1), and the isoenzymes CK 1-3 and LD 1-5, in acute myocardial infarction (AMI) is reviewed. Particular attention is given to electrophoretic analysis of the isoenzymes (and the CK isoforms/subforms) following AMI and thrombolytic therapy. Other protein markers for the monitoring of AMI, including myoglobin and muscle contractile proteins, are also discussed and the potential for the detection of new marker proteins using high-resolution two-dimensional electrophoretic methods is demonstrated. Whilst emphasis is placed upon electrophoretic methods the value of complementary immunoassays is acknowledged in order to maintain a balanced perspective.

Aspartate Aminotransferases↗

PubMed1991

The pharmacokinetics of total and unbound concentrations of tenoxicam in synovial fluid and plasma.

Tenoxicam is a nonsteroidal antiinflammatory drug with an elimination half-life of 60-80 hours; it is administered once daily. Tenoxicam concentrations were measured in plasma (10 samples) and synovial fluid (6 samples) over a 24-hour dosage interval at steady state in 10 subjects with arthritis who had been taking the drug at a dosage of 20 mg/day for at least 2 weeks. Total tenoxicam concentrations in synovial fluid were always less than those in plasma, and there was little fluctuation in plasma or synovial concentrations over the dosage interval, although there was substantial inter-subject variation in both concentrations. There was a significant relationship between the tenoxicam dosage when expressed as mg/kg of body weight and the average steady-state total concentration of tenoxicam in plasma (r = 0.80, P = 0.006); this accounted for a substantial proportion of the intersubject variation. The mean +/- SD steady-state concentrations in synovial fluid and plasma were 3.9 +/- 1.8 micrograms/ml and 9.2 +/- 3.7 micrograms/ml, respectively, yielding a mean +/- SD synovial fluid: plasma ratio of 0.43 +/- 0.12. Synovial fluid:plasma ratios of total tenoxicam correlated with synovial fluid:plasma ratios of albumin (r = 0.71, P = 0.02). The synovial fluid:plasma ratio of unbound tenoxicam was 0.90 +/- 0.3 (95% confidence interval 0.68-1.11), which was not significantly different from a value of 1 (t = -1.09, P = 0.31).

Adult↗

PubMed1991

Pharmacokinetics of the enantiomers of ibuprofen in the rabbit.

The stereoselective disposition of ibuprofen was studied in male New Zealand White (NZW) rabbits (n = 4) following an infusion (0.16 mg/kg/min) to steady-state of each of the enantiomers of ibuprofen with one week between treatments. The mean (+/- SEM) steady-state clearances of (R)-ibuprofen (15.5 +/- 1.1 ml/min/kg) and (S)-ibuprofen (13.6 +/- 1.9 ml/min/kg) were not significantly different from each other (p greater than 0.05) and exceeded the plasma clearance of indocyanine green (4.3 +/- 0.4 ml/min/kg) in a separate group of rabbits (n = 6). When the infusion rate of the enantiomers was doubled there was a significant decrease in the mean clearance of both (R)-ibuprofen (28%; p less than 0.018) and (S)-ibuprofen (24%; p less than 0.003). There was enantiospecific chiral inversion of (R)-ibuprofen to (S)-ibuprofen (fi = 0.30 +/- 0.07) as has been observed in all species so far studied for this 2-arylpropionic acid. The metabolic capacity for elimination of ibuprofen enantiomers was much greater than reported for either fenoprofen or ketoprofen and suggests that the clearance of ibuprofen enantiomers may be flow dependent in this species.

Animals↗

PubMed1991

Molecular asymmetry and its pharmacological consequences.

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Drug Monitoring↗

PubMed1990

Monoclonal antibodies against an HLA-B27-derived peptide react with an epitope present on bacterial proteins.

The role of molecular mimicry in the spondyloarthropathies was investigated with respect to the epitopes involved. mAb were produced against a synthetic peptide whose sequence was derived from a polymorphic region of the HLA-B27 molecule (amino acids 63-83). Two antibodies (J7F2 and H2B6) were selected for study on the basis of their ability to react with bacterial envelope proteins (ELISA) and B27-positive cells (immunofluorescence). J7F2 reacted preferentially with B27-positive cells and neither antibody reacted with MHC class I negative cells. Based on SDS-PAGE blot analysis of bacterial envelope proteins, the pattern of reactivity for both antibodies (against 36- and 19-kDa proteins) was the same as that for a third monoclonal produced against bacterial envelope and reactive with B27-positive cells. This apparent epitope similarity was investigated by using synthetic peptides to inhibit binding of the monoclonals. The B27 synthetic peptide and a smaller peptide derived from it were efficient inhibitors of antipeptide and antibacterial antibody binding to bacterial Ag and B27-positive cells. These studies provide insight into the molecular basis of cross-reactivity between bacterial proteins and MHC class I molecules.

Amino Acid Sequence↗

PubMed1990

Stereoselective disposition of ibuprofen and flurbiprofen in rats.

(R)-2-Arylpropionates are often inverted to the pharmacologically active S-enantiomers in vivo, although there is significant interspecies variability in inversion. In order to provide a basis for determining the biochemical consequences of this unique process using rats as a model, it was important to establish the pharmacokinetic disposition of the enantiomers of ibuprofen, a drug well inverted in man and flurbiprofen, a drug apparently poorly inverted in man. Rats were dosed i.v. with a single dose of (R)- or (S)-ibuprofen (20 mg/kg), (R,S)-ibuprofen (40 mg/kg), (R)- or (S)-flurbiprofen (10 mg/kg), or (R,S)-flurbiprofen (20 mg/kg). Each treatment group consisted of six animals. Serial blood samples were withdrawn over a period of 6 h for ibuprofen and 10 h for flurbiprofen. These drugs were assayed in plasma by a stereospecific HPLC assay. The pharmacokinetics of the ibuprofen and flurbiprofen enantiomers were evaluated using a two-compartment open model with conversion of the R- to S-enantiomers in the central compartment. There was 50 +/- 4% inversion of (R)-ibuprofen, a figure similar to that observed in man and (R)-ibuprofen had a higher clearance (12.6 +/- 1.3 ml/min/kg) than (S)-ibuprofen (7.7 +/- 0.7 ml/min/kg; P less than 0.01). The clearance of (R)-flurbiprofen after racemate (2.3 +/- 0.1 ml/min/kg) was higher than its clearance when administered alone (1.7 +/- 0.2 ml/min/kg; P less than 0.01), indicating a pharmacokinetic interaction between the enantiomers (most probably at plasma protein binding sites). A corresponding difference was not observed for ibuprofen. There was a small amount of inversion of (R)-flurbiprofen as determined by area analysis (4.5 +/- 1.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Enantiomers in arthritic disorders.

Drugs which have a center of asymmetry are often administered as an equal mixture of the two possible enantiomeric forms i.e. a racemate. However, there are frequently large pharmacodynamic and pharmacokinetic differences between enantiomers. Consequently, it is possible that while one enantiomer mediates the antiinflammatory or antirheumatic action, the other enantiomer, although adding little to the efficacy of the drug, may contribute to its adverse effects. Asymmetric drugs may also serve as sensitive pharmacological probes of the mechanisms underlying the action of drugs and the inflammatory processes which they modulate. These concepts are the focus for this review.

Arthritis↗