PubMed Health⌕ Search

Biomedical subjects

H Barnes

Publications and source records attributed to H Barnes.

18 recordsLinked to original sources
PubMed1996

Beyond CAGE. A brief clinical approach after detection of substance abuse.

Generalist physicians should incorporate alcohol and drug abuse detection and brief intervention in the care of their patients. A suggestion of alcohol or drug abuse or a positive response to the CAGE questions deserves further assessment such as clarification about adverse consequences, inquiry about loss of control, determination of the patient's perception of the substance use, and an assessment of the patient's readiness to change behavior. Brief intervention with the patient in the clinical setting about alcohol or drug use can be effective. Motivational interviewing, a directive, patient-centered counseling style for enhancing motivation for change, can make brief interventions more effective by incorporating the patient's readiness to address alcohol or drug use. A useful clinical approach is presented that is tailored to the patient's stage of readiness to change alcohol or drug abuse behavior.

Attitude to Health↗
PubMed1991

Right ventricular infarction: a clinical case study.

In this article we review the specific case of Mrs. F., a 63-year-old white woman who recently had classical right ventricular infarction associated with left ventricular inferior wall myocardial infarction. The presentation covers her medical history, clinical course pathophysiology of the right ventricular infarction, and goals of the medical modalities used in treatment. Nursing problems are identified specifically related to right ventricular infarcts, and treatment considerations are discussed. A brief conclusion recaps Mrs. F.'s discharge course and reviews some specific problems associated with right ventricular infarcts, of which critical care nurses need to be aware.

Cardiac Catheterization↗
PubMed1987

Intraspecies individuality for the metabolism of steroids.

A variety of regulatory factors contribute to differences in the rates of 6 beta-hydroxylation, 16 alpha-hydroxylation and 21-hydroxylation of progesterone as catalysed by liver microsomes prepared from individual rabbits. It is likely that the 6 beta-hydroxylation of progesterone is catalysed primarily by cytochrome P-450 3c, an enzyme that exhibits allosteric activation by alpha-napthoflavone, and by a form of P-450 3b, 6 beta+, that is expressed in some rabbits in an autosomal dominant manner. The mechanism of activation for P-450 3c appears to reflect an effector mediated increase of the affinity of the enzyme for substrate as judged by substrate binding studies. A second form of P-450 3b, 6 beta-, catalyses a major portion of hepatic progesterone 16 alpha-hydroxylation and exhibits activation by a variety of C21 steroids of which 5 beta-pregnane-3 beta,20 alpha-diol is the most efficacious. P-450 1, which catalyses the 21-hydroxylation of progesterone, is expressed at 10-fold higher levels in the 21H phenotype than the 21L phenotype, and the former is inherited as an autosomal dominant characteristic. A cDNA encoding a P-450 1-related gene product exhibits a predicted amino acid sequence that is 95% homologous to that of P-450 1. The P-450 1-related gene product is expressed in liver to a similar degree in both 21H and 21L rabbits.

Allosteric Regulation↗
PubMed1987

Studies on the metabolic fate of valproic acid in the rat using stable isotope techniques.

1. The metabolic fate of two specifically deuterated analogues of valproic acid (VPA), [2-2H1]VPA and [3,3-2H2]VPA, was studied in the rat following i.p. injection. 2. A total of 11 urinary metabolites of each labelled substrate were detected by g.l.c.-mass spectrometry. Those metabolites which resulted from oxidation of the drug at C-4 and/or C-5 retained the deuterium label(s), whereas products of oxidation at C-2 and/or C-3 exhibited varying degrees of deuterium loss. 3. The deuterium content of 3-hydroxy-VPA indicated that this metabolite has a dual origin, and arises in part by beta-oxidation of VPA and in part by direct hydroxylation at C-3. An apparent intramolecular isotope effect (kH/kD) of ca. 8 was associated with the latter process. 3-Oxo-VPA appeared to be formed mainly by oxidation of delta 2-VPA, rather than by oxidation of 3-hydroxy-VPA. 4. Evidence was obtained that delta 3-VPA is formed reversibly from delta 2-VPA, and that further desaturation of delta 3-VPA gives rise to a metabolite believed to have a 2,3'-diene structure. 5. The stable isotope method employed in this investigation represents a powerful technique for studies on the origin of drug metabolites and for the elucidation of complex metabolic inter-relationships in vivo.

Animals↗
PubMed1986

Rabbit endocervical epithelium: morphometric analysis of secretory cell populations.

In this report we quantitated ultrastructural changes in two cytologically distinct secretory cell populations from the rabbit endocervix. Type I and type II cells from estrous animals differ only in the presence of one or more empty cytoplasmic vacuoles in type II cells. Comparing type II cells from 5-day pseudopregnant (PSP) rabbits with type II cells from estrous controls, there is no increase (P greater than .05) in the average vacuole volume. When type I and type II cells from PSP animals are compared to cells from estrous controls, there is a decrease (P less than .01) in the average cell volume, a decrease (P less than .01) in the average nuclear volume, and a decrease (P less than .01) in the average granule volume. This reduction in the granule content of secretory endocervical cells was correlated with a dramatic decrease in protein glycosylation into the microsomal fraction. Serum estradiol concentrations for estrous (13.7 +/- 1.0 pg/ml) and PSP (18.1 +/- 1.5 pg/ml) animals were comparable. However, the 36-fold increase in serum progesterone concentrations for PSP (12.04 +/- 1.7 ng/ml) animals compared to estrous (0.33 +/- 0.1 ng/ml) animals may be responsible for the decrease in protein glycosylation.

Animals↗
PubMed1985

Multiple gene-like sequences related to the rabbit hepatic progesterone 21-hydroxylase cytochrome P-450 1.

Rabbits exhibit phenotypic differences, 21H and 21L, in the rate of hepatic progesterone 21-hydroxylation that reflect 10-fold higher microsomal concentrations of cytochrome P-450 1 in 21H rabbits. A cDNA library in pBR322 was prepared from liver mRNA isolated from a 21H rabbit. A clone, p1-8, producing a hybrid protein resulting from the insertion of the cDNA into the beta-lactamase gene of the plasmid expressed 5 distinct epitopes that were recognized by a panel of monoclonal antibodies developed toward P-450 1. RNAs selected from total hepatic mRNA by filter hybridization with p1-8 yield at least two electrophoretically distinct proteins when translated in vitro and immunoprecipitated with the 3C3 monoclonal antibody. Only one of the two proteins is recognized by the 1F11 monoclonal antibody, which is highly specific for P-450 1, and the immunoprecipitated protein exhibits the electrophoretic mobility of P-450 1. The other protein remains unidentified. Northern blot analysis indicates that the 3' noncoding portion of p1-8 hybridizes to higher steady state concentrations of polyadenylated RNA in the 21H as compared to 21L rabbits. This correspondence in expression with that of P-450 1 in the 21H and 21L phenotypes further suggests that p1-8 encodes P-450 1 or a closely related protein. The cDNA is 1871 base pairs in length and encodes a protein of 487 amino acids. Southern blot analysis indicates that several independent, gene-like sequences hybridize with the 3' noncoding region of p1-8 under conditions of high stringency. These results indicate that P-450 1 is a member of an extensive multigene family.

Amino Acid Sequence↗
PubMed1975

An improved method of assessing topical corticosteroid activity.

Topical application of ointment bases causes varying degrees of epidermal thickening in guinea-pigs. This is reproducible and can be accurately measured. Suppression of these changes was produced by addition of beta-methasone 17-valerate, fluocinolone acetonide, fluocinonide and hydrocortisone acetate. The inhibitory effect of these steroids was related to the type of corticosteriod, its concentration and the ointment base. The effect was still evident at extremely high dilutions of the steroids and could be measured at concentrations as low as 5 X 10(-5) % of fluocinonide in FAPG. This technique has the merits of being reproducible, sensitive and accurate. It should find a place among existing methods in assaying the efficacy of topical corticosteroids and in aiding in the selection of bases most suitable for formulation of these preparations.

Administration, Topical↗
PubMedDate not supplied

Enantioselective synthesis and preliminary metabolic studies of the optical isomers of 2-n-propyl-4-pentenoic acid, a hepatotoxic metabolite of valproic acid.

The enantiomers of 2-n-propyl-4-pentenoic acid (delta 4-VPA), a known hepatotoxic metabolite of 2-n-propylpentanoic acid (valproix acid, VPA), were synthesized with the aid of the chiral auxiliaries (4S)-4-(2-propyl)-2-oxazolidone and (4R,5S)-4-methyl-5-phenyloxazolidone. Alkylation of the n-valeryl derivatives of these oxazolidones with allyl bromide, followed by reductive cleavage and chromic acid oxidation of the product, afforded the desired acids, (R)- and (S)-delta 4-VPA. Greater than 93% enantiomeric excess was achieved in the preparation of both enantiomers. Preliminary studies on the metabolic fate of (R)- and (S)-delta 4-VPA in freshly isolated rat hepatocytes revealed striking differences in the biotransformation of the two enantiomers. Quantification of two major metabolites of delta 4-VPA, viz., 4,5-diOH-VPA gamma-lactone and 2-n-propyl-2(E),4-pentadienoic acid (delta 2E,4-VPA), indicated that larger amounts of the gamma-lactone were formed in incubations utilizing (R)-delta 4-VPA as substrate, whereas production of the diene was greater in incubations with (S)-delta 4-VPA. On the basis of the premise that delta 4-VPA serves as a mechanism-based irreversible inhibitor of enzymes of the fatty acid beta-oxidation complex, these differences in metabolism suggest that the two enantiomers of delta 4-VPA may differ in their hepatotoxic potential.

Animals↗
PubMedDate not supplied

Enantiotopic differentiation during the biotransformation of valproic acid to the hepatotoxic olefin 2-n-propyl-4-pentenoic acid.

The enantiomers of 2-[( 3-13C]-n-propyl)pentanoic acid [(R)- and (S)-[13C]VPA] were employed as metabolic probes to investigate stereochemical aspects of the biotransformation of valproic acid (VPA) to 2-n-propyl-4-pentenoic acid (delta 4-VPA), a hepatotoxic metabolite of VPA. When incubated with hepatocytes freshly isolated from untreated male rats, each labeled substrate (initial concentration 1.0 mM) underwent metabolism to [13C]-delta 4-VPA, the formation of which was time-dependent and occurred at a rate of ca. 20 ng/(10(6) cells.4-h incubation). Analysis of this unsaturated metabolite by GC-MS techniques revealed that, following incubation of (R)-[13C]VPA, desaturation had taken place preferentially (by a factor of approximately 4) on the labeled propyl group (i.e., on the R side chain). Parallel incubations with (S)-[13C]VPA supported this conclusion, in that metabolism of this isotopic variant of VPA led to a terminal olefin that also was predominantly (83 +/- 2%) of R configuration (in this case oxidized selectively on the unlabeled side chain). Hence, biotransformation of VPA to delta 4-VPA in rat hepatocytes occurs with marked enantiotopic differentiation, favoring production of the R enantiomer of this chiral metabolite. When rats were pretreated with phenobarbital (80 mg kg-1 day-1 ip for 3 days) prior to isolation of hepatocytes, the overall rate of metabolism of VPA to delta 4-VPA over the 4-h incubation period increased approximately 3-fold, while the degree of product enantioselectivity was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

British AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Mechanistic studies on the metabolic chiral inversion of R-ibuprofen in the rat.

Deuterium labeling techniques and stereoselective GC/MS methodology have been employed to investigate the mechanism by which R-ibuprofen undergoes metabolic chiral inversion in the rat in vivo. Following oral administration of a mixture of R-ibuprofen (7.5 mg kg-1) and R-[ring-2H4; 2-2H]ibuprofen (R-[2H5]ibuprofen) (7.5 mg kg-1) to male Sprague-Dawley rats, the enantiomeric composition and deuterium excess of the drug were determined in serial plasma samples and in pooled urine collected over 10 hr. The results demonstrate that: (i) R-ibuprofen undergoes extensive inversion of configuration to its S antipode in the rat; (ii) chiral inversion of R-[2H5]ibuprofen yields S-[2H4]ibuprofen in a process that involves quantitative loss of the deuterium atom present originally at C-2; (iii) labeling of R-ibuprofen with deuterium at C-2 does not introduce a measurable kinetic deuterium isotope effect on the chiral inversion reaction; and (iv) metabolism of R-[2H5]ibuprofen leads to the appearance in plasma and urine of molecules of R-ibuprofen labeled with 4 atoms of deuterium. On the basis of these findings, a mechanism is proposed for the chiral inversion reaction that invokes the stereoselective formation of the coenzyme A thioester of R-ibuprofen as a key metabolite; conversion of this species to the corresponding enolate tautomer affords a symmetrical intermediate through which racemization of ibuprofen occurs in vivo.

Animals↗