Dissecting the molecular mechanism of nuclear receptor action: transcription coactivators and corepressors

No abstract available.

Expression of a recombinant branched chain alpha-oxo acid dehydrogenase complex E2 (BCOADC-E2) in insect cells and its immunoreactivity to autoimmune sera

Preparation of a pure autoantigen by way of recombinant DNA technology has an important value in an accurate diagnosis or prognosis of an autoimmune disease. BCOADC-E2 subunit, a mitochondrial protein, has been known to be the autoantigen of primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, as well as idiopathic dilated cardiomypathy (IDCM), a chronic autoimmune heart disease. Recombinant form of this molecule had been expressed in E. coli but with low yield and severe degradation. Furthermore, sera from IDCM patients failed to recognized BCOADC-E2 molecule produced in prokaryotic expression system. In this study, a recombinant bovine BCOADC-E2 fusion protein has been expressed in insect cells using baculovirus expression system and analyzed anti-BCOADC-E2 reactivity in sera from patients with PBC or with IDCM. Optimal production of the recombinant fusion protein has been achieved at 20 multiplicity of infection (MOI), and the protein was affinity-purified using metal-binding resins. The affinity-purified BCOADC-E2 protein was successfully recognized by sera from PBC patients, but not by sera from IDCM patients suggesting that the different auto-immune response against BCOADC-E2 is needed to be elucidated in terms of epitope recognition.

Polyamines in the male reproductive system

This review covers some common aspects of the biosynthesis, interconversion pathways and biochemical functions of polyamines. A particular emphasis is given in experitemtal models as well as humans, to their presence in the male gonad, postate gland, seminal vesicles, epididymis and semen. The interaction between hormones (androgens, LH, FSH and PRL) and the main enzymes involved on the polymine biosynthesis, and the relationship of these compounds on cell growth and differentation, are also discussed. In this regard, an attention is offered to the potential role of polymines during early spermatogenesis stages and the use of some enzymed involved in their biosynthesis as sensitive and specific markers of the action of androgens and antiandrogens in the epididymis. Finally, a special issue is addressed to the controversial information documented on polymines, their oxidation products and the relationship with male fertility.

La biodiversidad humana y sus efectos sobre la variabilidad farmacologica: enzimas CYP2D6 y NAT2 en poblaciones amerindias de Panama, Colombia y Costa Rica / Human biodiversity and its effects on the pharmacological variability: CYP2D6 and NAT2 enzymes in Amerind populations of Panama, Colombia and Costa Rica

Human biodiversity originates partially from human microevolution, which have produced different populations. This biodiversity is responsible for most of the variability in drug response. We present the methodology employed in population pharmacology studies and general information about the CYP2D6 and NAT2 systems. We report results obtained in Embera and Ngawbe Amerindians, who are characterized by a low phenotypic and genotypic CYP2D6 diversity. In regard to NAT2, Amerindians are distinguished by a high allelic frequency of S3 and low ones of S1 and S2, situation which is reversed in Caucasians

Metabolism of 5-aminoquinoline with liver cytosol enzyme.

In vitro oxidation and acetylation of 5-aminoquinoline by rabbit liver enzyme preparation has been investigated. Incubation of 5-aminoquinoline with cytosol fraction of the enzyme preparation in the presence of acetyl coenzyme-A gave rise to three different products, viz. 5-amino-2-hydroxy quinoline, 5-acetyl-aminoquinoline and 5-acetylamino-2-hydroxy quinoline due to the combined action of aldehyde oxidase and N-acetyl transferase. The metabolites thus obtained by enzyme catalysed reactions were isolated and separated by TLC, HPLC and subsequently characterised by IR and mass spectral fragmentation techniques.

Estudio preliminar sobre el fenotipo de acetilador de los amerindios Teribes / Preliminar study on the phenotype of acetylator of Teribe Amerindians

El estudio de la capacidad de acetilación en 62 voluntarios teribes, procedentes de Sieykin, Sieyic y Santa Rosa, demonstró que 48.4% eran acetiladores rápidos y 51.6%, acetiladores lentos. Al comprobar estos resultados con los que obtuvimos en una población cuna, en la cual encontramos que el 78% era de acetiladores rápidos, se observa que tanto la distribución de los sujetos estudiados, según el porcentaje de isoniacida que acetilaron, como el porcentaje de acetiladores lentos y rápidos indican que, en ambos grupos, existen diferencias en la actividad de la N-acetiltransferasa. Estos resultados sugieren que pueden existir diferencias fundamentales entre los diferentes grupos amerindios, en la habilidade de biotransformar los medicamentos

A acetilaçäo da isoniazida na síndrome de Gilbert / Isoniazid acetylation in Gilbert's syndrome

O fenótipo acetilador da isoniazida foi investigada em 19 pacientes caucasóides portadores de síndrome de Gilbert, por intermédio da avaliaçäo do percentual de acetil-isoniazida na urina. A proporçäo de acetiladores lentos entre os pacientes com síndrome de Gilbert foi semelhante àquela verificada em um grupo controle de caucasóides. Conclui-se que na síndrome de Gilbert näo há interferência na capacidade hepática de acetilaçäo da isoniazida