Transporter genes ABCG2 rs2231142 and ABCB1 rs1128503 polymorphisms and atorvastatin response in Chilean subjects.

WHAT IS KNOWN AND OBJECTIVE: Statins are first-line therapy for reducing high cholesterol levels. However, response to these drugs shows high interindividual variability. We aimed to investigate the influence of two single nucleotide polymorphisms (SNP) (ABCB1 rs1128503 and ABCG2 rs2231142) in the ABC transporter genes on response to short-term low-dose atorvastatin in Chilean hypercholesterolaemic patients. METHODS: We studied 127 Chilean hypercholesterolaemic patients treated with 10 mg/d atorvastatin for 4 weeks. The lipid profile was determined before and after drug administration. Genotyping of the rs1128503 and rs2231142 variants was performed using TaqMan® Drug Metabolism Genotyping Assays. RESULTS AND DISCUSSION: Genotype distribution for all polymorphisms investigated was consistent with the Hardy-Weinberg equilibrium. Atorvastatin reduced TC, LDL-C and TG concentrations (P<.05), whereas HDL-C levels were found to be increased (P<.05). Minor allele frequencies for rs1128503 and rs2231142 variants were 0.453 and 0.075, respectively. In this study, patients prescribed with short-term low-dose atorvastatin and carrying ABCB1 (rs1128503) or ABCG2 (rs2231142) SNPs did not show differences in LDL-C response (P>.05). WHAT IS NEW AND CONCLUSION: The ABCB1 SNP was not associated with response to atorvastatin in Chilean subjects. The few ABCG2 421A homozygotes did not allow meaningful inferences to be made for this polymorphism.

Tricobezoar gástrico e intestinal en adolescente femenina de 15 años: a propósito de un caso clínico IVSS "Dr. Tulio Carnevali Salvatierra" Mérida-Venezuela / Gastric and intestinal trichobezoar female teenager about 15 years: a purpose of case clinical in IVSS Dr. Tulio Carnevali Salvatierra

Los tricobezoar son recolecciones de material ingerido (pelos, fibras) que se acumulasn en estómago e intestino. Se originan de la tricotilomanía más tricofagia, cuando el tricobezoar se acumula en duodeno recibe el nombre de Sídrome de Rapunzel, más frecuente en el sexo femenino. Adolescente de 15 años, quien presentó dolor abdominal de aparición insidiosa acompañada de naúseas y vómitos incontables que se irradian a hipocondrio y fosa iliaca izquierda, su evolución fue torpida presentando signos de irritación peritoneal. Se realiza laparatomía exploradora hallándose tumor de contenido de pelo a nivel del Ángulo de Treitz, y cámara gástrica. Siendo egresada y referida al servicio de psiquiatría infanto-juvenil.

The interface between an alternating CG motif and a random sequence motif displays altered nuclease activity.

Previously we described the B-Z junctions produced in oligomers containing (5meCG)4 segments in the presence of 5.0 M NaCl or 50 uM Co(NH3)6+3 [Sheardy, R.D. & Winkle, S.A., Biochemistry 28, 720-725 (1989); Winkle, S.A., Aloyo, M.C., Morales, N., Zambrano, T.Y. & Sheardy, R.D., Biochemistry 30, 10601-10606 (1991)]. The circular dichroism spectra of an analogous unmethylated oligomer containing (CG)4, termed BZ-IV, in 5.0 M NaCl and in 50 uM Co(NH3)+3 suggest, however, that this oligomer does not form a B-Z hybrid. BZ-IV possesses Hha I sites (CGCG) in the (CG)4 segment and an Mbo I site (GATC) at the terminus of the (CG)4 segment. BZ-IV is equally digestible in the presence and absence of cobalt hexamine by Hha I, further indicating that the structure of BZ-IV is fully B-like under these conditions. The Mbo I cleavage site at the juncture between the (CG)4 segment and the adjacent random segment displays enhanced cleavage by both Mbo I and its isoschizomer Sau3AI in the presence of cobalt hexamine. In addition, exonuclease III digestion of BZ-IV is inhibited at this juncture. Actinomycin inhibits Mbo I activity in the presence of cobalt hexamine but not in the absence. Together, these results suggest that enzymes recognize the interfaces of (CG)n and adjacent random sequences as altered substrates even in the absence of a B-Z junction formation.

Enhanced reactivity of a B-Z junction for cleavage by the restriction enzyme MboI.

We have been investigating the structure, dynamics, and ligand-binding properties of the interface that exists between a right-handed conformation and a left-handed conformation (i.e., a B-Z junction) in synthetic DNA oligomers. Since exo- and endonuclease activity is known to be sensitive to the conformation of the template DNA, we have designed and synthesized a DNA oligonucleotide of 20 base pairs (designated as BZ-III) with an MboI recognition site (GATC) at the location of a potential B-Z junction. The activity of the MboI enzyme toward this molecule and DNA oligomers that contain multiple MboI sites located at B-Z junctions was monitored in the absence and presence of the Z-conformation-inducing reagent cobalt hexaammine. In all cases, the activity of the enzyme was enhanced in the presence of cobalt hexaammine. The activity of MboI toward BZ-III, in the presence and absence of cobalt hexaammine, was also examined when the DNA oligomer is also in the presence of the DNA binding drugs actinomycin D, ametantrone, or ethidium bromide. In all cases, the activity of the enzyme was inhibited in the presence of drug. The results suggest that B-Z junctions are structurally unique and that this uniqueness may alter nuclease activity at sites in or near the junction.