INTERCAMBIO DE CROMÁTIDES HERMANAS INDUCIDOS POR EL TRATAMIENTO EN PACIENTES CON CÁNCER DE MAMA

Entre las terapias más utilizadas para tratar el cáncer mamario está la de Ciclofosfamida-Adriamicina(A/C), fármacos que ejercen efecto por disrupción del ADN que lleva a la muerte celular, lo que genera el control de la enfermedad; además de una gran cantidad de efectos adversos difíciles de sobrellevar para los pacientes

Modified procedure to assess dna breakage in spermatozoa by means of the comet assay

The comet assay is a relatively inexpensive, fast, sensitive and reliable method to detect DNA breakage upon individual cells. The most widely used cell type in this technique is lymphocyte, because they are easy to obtain and handle, and because they are continually exposed to xenobiotics that enter into the body. However, is important to consider the possibility to use other cell types for very specific purposes. Sperm cells are of special interest because they could be used as a biomonitor to risk assessment in populations occupationally exposed to xenobiotics. Besides, the fact that there are not functional DNA repair mechanisms in these cells could increase the sensitivity of the system. We present here several modifications to the comet assay methodology to evaluate DNA breakage in sperm cells with reliable results

Cinética de internalización del radiofármaco 99mTc-N2S2-TAT (49-57) Lys3-BN en linfocitos humanos empleando el ensayo cometa.

En México, el cáncer de mama representa la segunda causa de muerte en mujeres de 30 a 60 años, esto involucra un gran problema de salud pública. Por eso es importante contar con nuevas formas que nos permitan detectar el cáncer de mama en una etapa temprana. Una de las nuevas alternativas es por medio del uso de los radiofármacos de tercera generación, estos se emplean en medicina nuclear para obtener imágenes de blancos moleculares específicos y son únicos en su capacidad para detectar in vivo sitios bioquímicos, tales como receptores y enzimas.Introducción: Los receptores del péptido liberador de la gastrina (GRP-r) se sobreexpresan en cáncer de mama y próstata. La bombesina (BN) se une específica y fuertemente a GRP-r, esto es el fundamento para marcar la BN con radiación gamma. El TAT (49-57) es un péptido que penetra fácilmente la membrana celular por lo que, conjugado a diferentes proteínas, actúa como un “caballo de Troya” al aumentar la internalización de fármacos a la célula. El radiofármaco 99mTc-N2S2-TAT (49-57)-Lys3 -BN fue sintetizado con la finalidad de utilizarse en una etapa temprana de la carcinogénesis, para el diagnóstico y terapia del cáncer de mama. Objetivo: Determinar la internalización mediante el ensayo cometa del radiofármaco con y sin TAT, induciendo daño al DNA. Materiales y métodos: Se emplearon linfocitos humanos, con los siguientes protocolos: a) TATBN, b) 99mTc-Lys3 -BN; c) 99mTc-TAT (49-57)-Lys3 -BN y d) grupo control. Se realizó el ensayo cometa y se evaluó la cinética de internalización a 0, 5, 10, 15, 30 y 60 minutos en 3 repeticiones con cada uno, con actividades de 2.9, 6.6, 9.01 y 14.8 MBq. Se leyeron 100 células por tiempo y tratamiento, se determinó el Tail momento (TM). Se aplicó Kruscal-Wallis con p≤0.05 para la comparación entre los tratamientos. Resultados: El daño causado por el 99mTc-TAT-BN es mayor y diferente significativamente a los 30 minutos, respecto al control, mientras que 99mTc-BN y TAT-BN no los son. Conclusiones: Esto demuestra que el TAT-BN favorece la internalización del radiofármaco

Current Panorama of Dental Caries

The possibility of decreasing the risk of developing caries from the sort of diet is being tried consulting an internet database created by expert dentistsDental caries is a dynamical, multifactorial, commonly chronical process that affects one or several zones on the tooth surface. In 2012, WHO reported that 60-90% of the children and almost 100% of the adults in the world had dental caries. In Mexico, the System of Epidemiological Monitoring of Oral Pathologies (2015) reported that in a number of states, 93.2% of the population had dental caries. This review stresses that at present, additional to the classic factors involved in the etiology of dental caries, the participation of socioeconomic, educational, physiological factors as well genetic predisposition are considered; also, its association with systemic diseases, type 2 diabetes, for example, and with serum levels of iron and ferritin in children. Regarding diagnosis, the determination of serum iron level is considered, as well as the use of Diagnodent and digital infrared transilluminator. For the treatment of dental caries, antimicrobial photodynamical therapy, ozone therapy and peptide P11-4are proposed. Nowadays, in order to prevent caries in child population, the application of the Basic Research Factors Questionnaire (BRFQ) is proposed.COMECY

Polymorphisms GSTT1, GSTM1 and GSTP1 influence in magnitude of DNA damage induced by cyclophosphamide

The differences in tail length between this “wild type group” and the other 11 genotypes recognized were statistically significant, suggesting a relation between GST genotype and cyclophosphamide induced DNA damage modulation.Cancer is one of the major causes of death worldwide and one of the factors associated with this is the therapeutic failure. Recently there has been an increasing interest in designing personalized therapies based on patient’s genotype. Glutathione–S-Transferase genes GSTT1, GSTM1 and GSTP1 genes help in detoxification of various genotoxic agents such as cyclophosphamide, an indirect alkylating agent that damages the chemical structure of DNA. It is widely used with other drugs in the treatment of various cancers. Determine whether the extent of DNA damageevaluated by the comet assay performed in vitro by cyclophosphamide in lymphocytes is modulated by polymorphisms of GSTT1, GSTM1 and GSTP1. Lymphocytes from 120 healthy donors were treated with a single concentration of cyclophosphamide and the extent of DNA damage was evaluated by a modified comet assay. Polymorphisms of GSTT1 and GSTM1 were identified by end-point polymerase chain reaction, while GSTP1 alleles were identified by PCR-RFLP. A great variability in the response to cyclophosphamide was found among individuals. Only 12 individuals from all the volunteer donors showed to have the complete wild genotype (GSTT1, GSTM1, GSTP1Ile/Ile105, Ala/Ala114) and coincidentally, this was the group with the lowest cyclophosphamide produced DNA damageCOMECY

POLYMORPHISMS OF GSTM1, GSTT1 AND GSTP1 AND THEIR POSSIBLE ASSOCIATION WITH THE DEVELOPMENT OF DENTAL CARIES. PILOT STUDY

The results show the possible association between GST polymorphisms and the susceptibility to develop dental caries due to alteration of the enzymatic activity, this provides evidence that the genetic load may be a risk factor to dental caries.Objective: The purpose of this investigation was to study the relationship between the polymorphisms of GSTM1, GSTT1 and GSTP1 with the susceptibility to dental caries in Mexican. Methods: In a group of 64 individuals, the DMFT index and GST polymorphisms were determined and related. Results: The frequencies for GSTM1 were 48.4% with the wild allele and 51.6% null, with a mean DMFT of 6.1 and 5.5 respectively. For GSTT1 were 73.4% with the wild allele and 26.6% null, with a mean DMFT of 6.6 and 5.8, respectively. In GSTP1 exon 5, 23.4% with the wild allele, 53.2% (a/b) and 23.4% (b/b), the mean DMFT was 4.3, 6.6 and 5.9 respectively. 100% had the GSTP1 exon 6 wild genotype, with a mean DMFT of 6.4%. In the combined genotypes, the lower DMFT corresponds to the GSTM1 wild type genotype, GSTT1 wild type, GSTP1 exon 5 wild type, GSTP1c wild type and the highest DMFT value to GSTM1 null genotype; GSTT1 null; GSTP1 exon 5 a/b; GSTP1 exon 5 a/a.COMECY

Importance of the identification of the CYP3A4*2 polymorphism for the prescription of pharmacological treatment

The CYP3A4*2 polymorphism is rare in the population studied. Given the low frequency of CYP3A4*2 polymorphisms found in homozygous or heterozygous condition, it is advisable to consider the genotype of the patient before prescribing drugs metabolized by this gene.Variability in response to drugs is a problem in clinical practice. The rate of patients who respond adequately to pharmacological therapy is generally around 60. The CYP450 multienzyme complex is a microsomal system located in the endoplasmic reticulum. The enzymes participate in phase I metabolism of xenobiotics. CYP3A4 is the isoenzyme mostly expressed in liver. Its gene is polymorphic, of which CYP3A4*1A is the wild allele and CYP3A4*2 is a polymorphism which consists of the S222P substitution in the amino acid sequence, affecting the activity of the enzyme. Methods: In this study, we determine the frequency of CYP3A4*2 polymorphism in Mexican individuals. 62 apparently healthy individuals, from Toluca de Lerdo, Mexico. The sample was 3 mL of peripheral blood. The DNA was extracted and PCR-RFLPs were performed. Results:58 individuals possess the wild allele in homozygosity CYP3A4*1A/CYP3A4*1A (94%) and 4 individuals were heterozygous CYP3A4*1A/CYP3A4*2 (6%). The homozygous polymorphic CYP3A4*2/CYP3A4*2 was not found in any individual.COMECY

Mechanical Stimulation of Cells Through Scaffold Design for Tissue Engineering

Tissue engineering scaffolds attempt to mimic the stem cell environment by creating different biophysical and chemical signals. On the other hand, stem cells are able to sense these characteristics and change their destiny. Scientists try to explain these phenomena through scaffold design and in vitro experiments, but the mechanisms implicated remain unclear. Moreover, environment-cell interactions are a key process to get organs and tissues arrangement. Therefore, this chapter deals with the mechanical signals and mechanism involved in cell behaviour through scaffolds as a strategy in tissue engineering

Lineamientos para la elaboración del protocolo de investigación

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