Ángela Roco

In vitro biocontrol activity of Trichoderma harzianum on Alternaria alternata in the presence of growth regulators

EJB Electronic Journal of Biotechnology ISSN: 0717-3458 Vol.4 No.2, Issue of August 15, 2001© 2001 by Universidad Catolica de Valparaiso -- Chile Received November 30, 2000 / Accepted April 23, 2001

Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the Chilean population: comparison with Caucasian and Asian populations

Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxicity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4*17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5*3(0.76) and CYP2C9*3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(0.32), CYP1A2*1F(0.77), CYP3A4*1B(0.06), CYP2D6*2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19*2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6*4(0.04), CYP2C8*3(0.06), CYP2C9*2(0.06), CYP2D6*4(0.12), CYP2E1*5B(0.14), CYP2E1*6(0.19), and UGT2B7*2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be considered in the pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed populations and for drugs with a narrow safety range.

Oligosaccharides released by pectinase treatment of Citrus limon seedlings are elicitors of the plant response

Abstract Oligosaccharides of different sizes were released from intact Citrus limon seedlings treated with endopolygalacturonase obtained from Alternaria alternata . Also, an increase of phenylalanine ammonia lyase (PAL) activity and the formation of a phytoalexin, were observed. Only mechanically damaged, but not intact seedlings, were able to increase their PAL activity and to synthesize a phytoalexin, in response to isolated oligomers released from plant cell walls or obtained from polygalacturonic acid (PGA). The active oligomers (pectic fragments obtained from cell walls or pectic fragments obtained from PGA) contained between 17 and 23, or 13 to 20 units of galacturonic acid, respectively. Maximal PAL activation was obtained after 20 hr treatment of intact seedlings with endopolygalacturonase and after 7 or 4 hr of treatment of damaged seedlings with endopolygalacturonase or oligosaccharides, respectively. Also, as a result of the increase of PAL activity, the appearance of a phytoalexin was observed, always after 42 hr of PAL activation. Immunoprecipitation with PAL antibodies confirmed that PAL activation was due to an increase in the amount of enzyme.

Can pharmacogenetics explain efficacy and safety of cisplatin pharmacotherapy

Several recent pharmacogenetic studies have investigated the variability in both outcome and toxicity in cisplatin-based therapies. These studies have focused on the genetic variability of therapeutic targets that could affect cisplatin response and toxicity in diverse type of cancer including lung, gastric, ovarian, testicular, and esophageal cancer. In this review, we seek to update the reader in this area of investigation, focusing primarily on DNA reparation enzymes and cisplatin metabolism through Glutathione S-Transferases (GSTs). Current evidence indicates a potential application of pharmacogenetics in therapeutic schemes in which cisplatin is the cornerstone of these treatments. Therefore, a collaborative effort is required to study these molecular characteristics in order to generate a genetic panel with clinical utility.

Perception of the Usefulness of Drug/Gene Pairs and Barriers for Pharmacogenomics in Latin America

Pharmacogenetics and Pharmacogenomics areas are currently emerging fields focused to manage pharmacotherapy that may prevent undertreatment while avoiding associated drug toxicity in patients. Large international differences in the awareness and in the use of pharmacogenomic testing are presumed, but not well assessed to date. In the present study we review the awareness of Latin American scientific community about pharmacogenomic testing and the perceived barriers for their clinical application. In order to that, we have compiled information from 9 countries of the region using a structured survey which is compared with surveys previously performed in USA and Spain. The most relevant group of barriers was related to the need for clear guidelines for the use of pharmacogenomics in clinical practice, followed by insufficient awareness about pharmacogenomics among clinicians and the absence of regulatory institutions that facilitate the use of pharmacogenetic tests. The higher ranked pairs were TPMT/thioguanine, TPMT/azathioprine, CYP2C9/warfarin, UGT1A1/irinotecan, CYP2D6/amitriptiline, CYP2C19/citalopram and CYP2D6/clozapine. The lower ranked pairs were SLCO1B1/simvastatin, CYP2D6/metoprolol and GP6D/chloroquine. Compared with USA and Spanish surveys, 25 pairs were of lower importance for Latin American respondents. Only CYP2C19/esomeprazole, CYP2C19/omeprazole, CYP2C19/celecoxib and G6PD/dapsone were ranked higher or similarly to the USA and Spanish surveys. Integration of pharmacogenomics in clinical practice needs training of healthcare professionals and citizens, but in addition legal and regulatory guidelines and safeguards will be needed. We propose that the approach offered by pharmacogenomics should be incorporated into the decision-making plans in Latin America.

Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival

OBJECTIVE Prognostic biomarkers that distinguish between patients with good or poor outcome can be used to guide decisions of whom to treat and how aggressively. In this sense, several groups have proposed genetic polymorphisms as potential susceptibility and prognostic biomarkers; however, their validity has not been proven. Thus, the main goal of the present work was to investigate the potential role of single and combined CYP1A1, GSTM1, and GSTT1 genotypes as modifiers of cancer survival in Chilean patients with prostate cancer. METHODS AND MATERIALS A total of 260 histologically confirmed patients were recruited from a voluntary screening, and genomic DNA was obtained from their blood samples for genotyping analyses to detect the CYP1A1*2A polymorphism and GSTM1 and GSTT1 deletions. The progression of illness and mortality were estimated with a median follow-up of 8.82 years. Adjusted estimated genotype risks were evaluated by hazard ratio and 95% CI using the Cox proportional model. In addition, the Kaplan-Meier survival method and log-rank test were used to evaluate patient survival with regard to genotype. RESULTS The 9-year overall and specific survival rates were 67.6% and 36.6% in the GSTT1null group, 67.6% and 58.7% in the GSTM1non-null group, 69.0% and 51.6% in the *1A/*2A group, 63.9% and 61.5% in the *2A/*2A group vs. 76.2% and 62.3% in the GSTT1non-null group, 82.3% and 50% in the GSTM1null group, and 83.7% and 56.3% in the *1A/*1A group, respectively. The hazard ratios and the Kaplan-Meier curve results demonstrate that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes are significantly associated with mortality. Our study has two main limitations: a relatively small sample size and a low global mortality percentage (25.4%); thus, we need to continue the follow-up to confirm these findings. CONCLUSIONS Our results suggest that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes may be good prognosis markers, particularly in patients with high-risk tumors.

ANTIBODIES AGAINST FUNGAL CONIDIA AND ANTIBIOTICS INHIBIT PHENYLALANINE AMMONIA-LYASE ACTIVATION IN CITRUS

Summary Antibodies raised against Trichoderma harzianum conidia prevented accumulation of Phenylalanine ammonia-lyase (PAL, E.C. 4.3.1.5.) in Citrus . The observed effect of the antibodies is produced by a delay in the formation of the fungal germination tube. An increase of PAL activity of ca. 7 fold in C. limon and C. sinensis seedlings, and of ca. 2 fold in C. paradisii seedlings was found, as an hypersensitive response to inoculation with T. harzianum conidia. This increase in activity was due to «de novo« synthesis of the enzyme as demonstrated by the effect of protein-synthesis inhibitors and by immunotitration.

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica

Pharmacogenetics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well as the drug-target interaction. Therefore, the presence of allelic variants will classify people as poor, extensive or rapid/ultra rapid metabolizers, modifying drug efficacy and safety. In this work, the state of art in relation to this discipline is presented and the genetic variants of enzymes that are involved in drug pharmacokinetics or pharmacodynamics are described. The effects of these variants on the therapeutic response to drugs used in our country are also discussed.

Determinación del polimorfismo de CYP2C9*2 y su relación con la farmacocinética de acenocumarol en voluntarios sanos

Resumen:Antecedentes: La mayoria de los pacientes que reciben tratamientos con anticoagulantes orales por periodos prolongados presentan variabilidad en la respuesta. El acenocumarol es el anticoagulante oral mas prescrito en nuestro pais, es biotransformado principalmente por CYP2C9 e investigaciones re-cientes demuestran que la variante CYP2C9*2 es una de las responsables de la variabilidad de res-puesta a acenocumarol. Objetivo: Determinar las diferencias en los para-metros farmacocineticos de acenocumarol en volun-tarios que presentan la variante alelica CYP2C9*2. Metodos: Se estudiaron 24 voluntarios sanos. La deteccion de genotipos se realizo mediante PCR-RFLP y los parametros farmacocineticos se obtuvieron mediante la concentracion plasmatica de acenocumarol usando un metodo validado para UPLC-MS/MS. Resultados: Del total de 24 voluntarios, 19 tenian el genotipo CYP2C9*1/*1 (wt/wt), 4 te-nian genotipo CYP2C9*1/*2 (heterocigoto) y 1 voluntario tenia genotipo de CYP2C9*2/*2 (homocigoto recesivo). Los parametros farma-cocineticos del acenocumarol no fueron signifi-cativamente diferentes entre los individuos con genotipo CYP2C9*2 y CYP2C9*1. Sin embargo, la farmacocinetica de acenocumarol del individuo CYP2C9*2/*2 mostro diferencias relevantes con respecto a la observada en el grupo CYP2C9*1/*1 (tmax aumento 1,4 veces, ke disminuyo 1,8 veces y t1/2 aumento 1,7 veces).

Impacto de Ia Telemedicina en Ia calidad del Control de Tratamiento Anticoagulante Oral

Antecedentes: En el ano 2014 se inicio Telemedicina desde el Policlinico de Tratamiento Anticoagulante oral del Hospital San Juan de Dios y el Hospital de Curacavi, evitando asi el traslado de pacientes a Santiago para el control con el medico especialista. Metodos: Se utilizo licencia de video conferencia en el Hospital San Juan de Dios, dispositivo movil, equipo de INR capilar y stock de Acenocumarol en el Hospital de Curacavi. Resultados: En total se han realizado 2.174 consultas via Telemedicina (junio 2014 a diciembre 2015). Esta estrategia ha sido bien evaluada por los pacientes. La mejora en la calidad del tratamiento ha sido evidente: 58,3% de los pacientes del Hospital de Curacavi se encuentran en rango terapeutico, superior al 50,8% de los pacientes del Hospital San Juan de Dios (p < 0,05). En cuanto al Tiempo en Rango Terapeutico (TTR) 50,6% de los pacientes del Hospital de Curacavi se encuentran en rango versus 46,2% de los pacientes del Hospital San Juan de Dios (p< 0,05). Conclusiones: La Telemedicina utilizada por equipos comprometidos es capaz de mantener indicadores de calidad de la atencion que la validan como herramienta de atencion clinica a distancia. La Telemedicina, en cuanto es una herramienta que acerca el especialista a comunidades alejadas de centros hospitalarios complejos, es valorada y muy bien calificada por los usuarios.