Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 98
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
BMC Cancer ; 21(1): 1030, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34525956

RESUMO

BACKGROUND: Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3-4 toxicity. METHODS: Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. RESULTS: Reported grade ≤ 2 and 3-4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70-10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19-1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. CONCLUSION: Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos de Platina/administração & dosagem , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Idoso , Capecitabina/efeitos adversos , Estudos de Casos e Controles , Intervalos de Confiança , Proteínas de Ligação a DNA/genética , Di-Hidrouracila Desidrogenase (NADP)/genética , Endonucleases/genética , Feminino , Fluoruracila/efeitos adversos , Frequência do Gene , Genes p53 , Genótipo , Glutationa S-Transferase pi/genética , Glicina Hidroximetiltransferase/genética , Humanos , Leucovorina/efeitos adversos , Modelos Logísticos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Complexos Multienzimáticos/genética , Nomogramas , Razão de Chances , Compostos Organoplatínicos/efeitos adversos , Orotato Fosforribosiltransferase/genética , Orotidina-5'-Fosfato Descarboxilase/genética , Pirimidinas , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Proteína Grupo D do Xeroderma Pigmentoso/genética
2.
Biol Res ; 54(1): 13, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879265

RESUMO

BACKGROUND: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. RESULTS: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41-5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63-2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80-3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40-21.33, p = 4.1 × 10- 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13-0.10, p = 0.03). CONCLUSIONS: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.


Assuntos
Infecções por Helicobacter , Proteína Adaptadora de Sinalização NOD1/genética , Neoplasias Gástricas , Estudos de Casos e Controles , Ilhas Genômicas , Infecções por Helicobacter/genética , Helicobacter pylori , Humanos , Neoplasias Gástricas/genética
3.
Int J Mol Sci ; 23(1)2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35008894

RESUMO

Gastric cancer (GC) is the fifth leading cause of cancer deaths in the world, with variations across geographical regions and ethnicities. Emerging evidence indicates that miRNA expression is dysregulated in GC and its polymorphisms may contribute to these variations, which has yet to be explored in Latin American populations. In a case-control study of 310 GC patients and 311 healthy donors from Chile, we assessed the association of 279 polymorphisms in 242 miRNA genes. Two novel polymorphisms were found to be associated with GC: rs4822739:C>G (miR-548j) and rs701213:T>C (miR-4427). Additionally, rs1553867776:T>TCCCCA (miR-4274) and rs12416605:C>T (miR-938) were associated with intestinal-type GC, and rs4822739:C>G (miR-548j) and rs1439619:T>G (miR-3175) with TNM I-II stage. The polymorphisms rs6149511:T> TGAAGGGCTCCA (miR-6891), rs404337:G>A (miR-8084), and rs1439619:T>G (miR-3175) were identified among H.pylori-infected GC patients and rs7500280:T>C (miR-4719) and rs1439619:T>G (miR-3175) were found among H. pylori cagPAI+ infected GC cases. Prediction analysis suggests that seven polymorphisms could alter the secondary structure of the miRNA, and the other one is located in the seed region of miR-938. Targets of miRNAs are enriched in GC pathways, suggesting a possible biological effect. In this study, we identified seven novel associations and replicated one previously described in Caucasian population. These findings contribute to the understanding of miRNA genetic polymorphisms in the GC pathogenesis.


Assuntos
Biomarcadores Tumorais/genética , Infecções por Helicobacter/complicações , MicroRNAs/genética , Neoplasias Gástricas , Adulto , Estudos de Casos e Controles , Chile/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/genética
4.
Rev Med Chil ; 149(5): 724-732, 2021 May.
Artigo em Espanhol | MEDLINE | ID: mdl-34751325

RESUMO

BACKGROUND: Vitamin K antagonists such as acenocoumarol and warfarin are usually indicated for the treatment of Atrial Fibrillation (AF). The Therapeutic Range Time (TRT) is a quality of treatment indicator. Values greater than 65% are associated with significantly lower stroke and bleeding rates. Proper pharmaceutical care improves TRT. AIM: To evaluate the impact of pharmaceutical care in patients with AF treated with acenocoumarol. MATERIAL AND METHODS: We studied 41 patients using acenocoumarol for AF aged 71 ± 11 years (43% women). They received pharmaceutical counseling during 12 weeks. TRT was calculated retrospectively for the year before counseling and prospectively during the intervention period. RESULTS: After receiving pharmaceutical counseling TRT improved from 29% at baseline to 46% at the end of the intervention (p < 0.01). After pharmaceutical care, the adherence of patients to drug treatment improved from 27% at baseline to 85% at the end of the study. The user satisfaction survey of the pharmaceutical care received showed a high degree of patient satisfaction. CONCLUSIONS: Pharmaceutical care in patients with oral anticoagulant treatment improves TRT of anticoagulation. It is accepted and positively evaluated by patients.


Assuntos
Fibrilação Atrial , Preparações Farmacêuticas , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Aconselhamento , Feminino , Humanos , Masculino , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle
5.
Pharmacogenomics J ; 20(1): 136-158, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31616044

RESUMO

Colorectal cancer is one of the leading causes of cancer death worldwide. Over the last decades, several studies have shown that tumor-related genomic alterations predict tumor prognosis, drug response, and toxicity. These observations have led to the development of several therapies based on individual genomic profiles. As part of these approaches, pharmacogenomics analyses genomic alterations which may predict an efficient therapeutic response. Studying these mutations as biomarkers for predicting drug response is of a great interest to improve precision medicine. We conduct a comprehensive review of the main pharmacogenomics biomarkers and genomic alterations affecting enzyme activity, transporter capacity, channels, and receptors; and therefore the new advances in CRC precision medicine to select the best therapeutic strategy in populations worldwide, with a focus on Latin America.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Frequência do Gene/genética , Redes Reguladoras de Genes/genética , Farmacogenética/métodos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Frequência do Gene/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos
6.
Mol Biol Rep ; 47(11): 9239-9243, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33128686

RESUMO

Genetic variants are considered risk factors for gastric cancer. To date, 61 polymorphisms have been identified as associated with this disease. The aim of the present study was to analyze the association of some of those polymorphisms with GC in Chile. We performed a case-control study including 310 gastric cancer cases and 311 controls to assess the association of 36 single-nucleotide polymorphisms genotyped by Global Screening Array (GSA). Three polymorphisms was significantly associated: PSCA rs2294008 (allele model, OR = 1.49, 95%CI 1.17-1.88, P = 1.08 × 10-3), IL-4 rs2243250 (allele model, OR = 1.28, 95%CI 1.01-1.62, P = 0.04), and MUC1 rs4072037 (allele model, OR = 0.78, 95%CI 0.61-0.99, P = 0.04).PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in Chile. It suggests that those polymorphisms could be used as biomarkers to assess the genetic risk for this cancer outside of the previously studied populations, not only for East Asians and Caucasians populations.


Assuntos
Antígenos de Neoplasias/genética , Predisposição Genética para Doença/genética , Interleucina-4/genética , Mucina-1/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Chile , Feminino , Proteínas Ligadas por GPI/genética , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
7.
Int J Food Sci Nutr ; 71(3): 388-393, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31530040

RESUMO

Mexico ranks 2nd in adult obesity and 4th in milk intake worldwide. Low levels of IGF-1 have been related to obesity and can be reverted by milk intake. The rs6214 polymorphism has been associated with an increase in the expression of IGF-1. Therefore, the aim of the study was to evaluate the association between both, rs6214 polymorphism and milk intake, and obesity. We analysed 99 adult volunteers, with and without a history of milk intake, for the presence of this polymorphism through qPCR and body composition by electro-bioimpedance. Univariate logistic regression analyses showed that TT genotype is inversely associated with obesity and body fat mass. Besides, milk intake is also related to low obesity, body fat mass and visceral fat, and high percentage of lean mass. Multivariate logistic regression analyses confirm the univariate relationships, showing a clear inverted association between TT genotype, milk intake and obesity.


Assuntos
Dieta , Fator de Crescimento Insulin-Like I/genética , Leite , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adulto , Animais , Composição Corporal/genética , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , México , Pessoa de Meia-Idade , Adulto Jovem
8.
Int J Mol Sci ; 21(14)2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32650499

RESUMO

The urinary arsenic metabolites may vary among individuals and the genetic factors have been reported to explain part of the variation. We assessed the influence of polymorphic variants of Arsenic-3-methyl-transferase and Glutathione-S-transferase on urinary arsenic metabolites. Twenty-two groundwater wells for human consumption from municipalities of Colombia were analyzed for assessed the exposure by lifetime average daily dose (LADD) (µg/kg bw/day). Surveys on 151 participants aged between 18 and 81 years old were applied to collect demographic information and other factors. In addition, genetic polymorphisms (GSTO2-rs156697, GSTP1-rs1695, As3MT-rs3740400, GSTT1 and GSTM1) were evaluated by real time and/or conventional PCR. Arsenic metabolites: AsIII, AsV, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured using HPLC-HG-AFS. The influence of polymorphic variants, LADD and other factors were tested using multivariate analyses. The median of total arsenic concentration in groundwater was of 33.3 µg/L and the median of LADD for the high exposure dose was 0.33 µg/kg bw/day. Univariate analyses among arsenic metabolites and genetic polymorphisms showed MMA concentrations higher in heterozygous and/or homozygous genotypes of As3MT compared to the wild-type genotype. Besides, DMA concentrations were lower in heterozygous and/or homozygous genotypes of GSTP1 compared to the wild-type genotype. Both DMA and MMA concentrations were higher in GSTM1-null genotypes compared to the active genotype. Multivariate analyses showed statistically significant association among interactions gene-gene and gene-covariates to modify the MMA and DMA excretion. Interactions between polymorphic variants As3MT*GSTM1 and GSTO2*GSTP1 could be potential modifiers of urinary excretion of arsenic and covariates as age, LADD, and alcohol consumption contribute to largely vary the arsenic individual metabolic capacity in exposed people.


Assuntos
Arsênio/química , Arsênio/metabolismo , Glutationa Transferase/genética , Água Subterrânea/química , Metiltransferases/genética , Polimorfismo Genético/genética , Adulto , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/urina , Arsênio/urina , Arsenicais/urina , Ácido Cacodílico/urina , Exposição Ambiental/efeitos adversos , Feminino , Genótipo , Humanos , Masculino
9.
Pharmacogenet Genomics ; 29(7): 159-166, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31107374

RESUMO

BACKGROUND: Testicular cancer (TCa) is a malignant tumor with highest incidence and mortality rates in Chile. The genes coding for cytochrome P450, glutathione-S-transferases (GSTs), and UDP glucuronyl transferases (UGT) participate in the biotransformation and detoxification of xenobiotics. Mutations in these genes have been associated with a high incidence of various types of cancer and an increased risk of presenting adverse reactions to drugs. OBJECTIVE: The aim of this study was to relate the presence of genetic polymorphisms in cytochrome P450 1A1 (CYP1A1), CYP3A4, GSTM1, GSTP1, GSTT1, and UGT1A1 genes and nongenetic factors with the risk of developing TCa. METHODS: A total of 276 volunteers from the Chilean general population and 251 Chilean TCa patients were recruited for the study. Genotypic analyses were performed using qPCR and PCR-RFLP. RESULTS: Variant alleles found to increase the risk of developing TCa were CYP1A1*2C (rs1048943), GSTP1 (rs1695), and GSTT1null, especially when in conjunction with a cancer family history and/or a smoking habit. The results of the multivariate analysis showed that the presence of variant alleles of GSTP1 (rs1695) together with a smoking habit and a family history of cancer accounted for a 15.9% risk of developing TCa in the Chilean population. CYP1A1*2C, GSTM1null, GSTT1null, and GSTP1 (rs1695) are statistically related to the risk of appearance of TCa, alone or associated with nongenetic factors. CONCLUSION: Therefore, phase I and II variant alleles might be useful in evaluating susceptibility to TCa in the studied population.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Sistema Enzimático do Citocromo P-450/genética , Glucuronosiltransferase/genética , Glutationa Transferase/genética , Fumar/epidemiologia , Neoplasias Testiculares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Chile , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fumar/efeitos adversos , Fumar/genética , Adulto Jovem
10.
Rev Med Chil ; 147(10): 1273-1282, 2019 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-32186635

RESUMO

BACKGROUND: INR is used to monitor the treatment with vitamin K antagonists. A strategy to reduce waiting times for sampling is to measure INR in a capillary sample using a portable point of care (POC) type coagulometer. AIM: To evaluate the correlation of CoaguChek Pro II™, Xprecia™ and microINR™ with venous INR measured at the clinical laboratory and their ease of use. MATERIALS AND METHODS: Patients provided capillary and venous blood samples for parallel tests comparing Xprecia™ Stride with CoaguChek Pro II™ and with venous INR, microINR™ with CoaguChek Pro IITM and with venous INR. The devices' ease of use was assessed surveying the sampling staff. RESULTS: The three tested devices had good correlation coefficients with venous INR: CoaguChek Pro IITM 0.953 and 0.962; Xprecia™ of 0.912 and microINR™ of 0.932. The correlation coefficient of Xprecia™ with CoaguChek Pro IITM was 0.937 and microINR™ with CoaguChek Pro IITM was 0.976. CONCLUSIONS: CoaguChek Pro IITM, Xprecia™ and microINR™ results had a good correlation coefficient with INR measured at the laboratory. Our results indicate that, in the hands of trained users, POC-type coagulometers are reliable and acceptable for routine use in anticoagulant treatment control.


Assuntos
Coeficiente Internacional Normatizado/instrumentação , Sistemas Automatizados de Assistência Junto ao Leito/normas , Idoso , Anticoagulantes/uso terapêutico , Capilares , Chile , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/normas , Feminino , Humanos , Coeficiente Internacional Normatizado/normas , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Reprodutibilidade dos Testes , Tromboplastina/uso terapêutico
11.
J Diagn Med Sonogr ; 35(3): 189-197, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31131376

RESUMO

The craniocaudal (CC) length of the right lobe of the liver (RLL), liver texture, size of the main portal vein, and hemodynamics of the hepatic artery, were sonographically evaluated in female diabetic and non-diabetic patients. A One-way ANOVA, a Tukey's post-hoc test, and a Kruskal-Wallis with post-hoc Dunn's test, were employed. Non-symptomatic differences in liver anatomy were detected among non-controlled type 2 diabetes patients. They exhibited the longest CC length of the RLL (p = 0.04) as well as an enlarged main portal vein (p = 0.04). Hepatic artery resistive index (RI) was higher among controlled type 2 diabetes patients (p = 0.04). These differences were not attributed to fatty infiltration. Non-controlled type 2 diabetes patients exhibited significantly higher alanine aminotransferase, lower high-density lipoprotein cholesterol, and higher triglyceride levels, than in non-type 2 diabetes patients. Longitudinal sonography may provide valuable diagnostic information in the management of type 2 diabetes.

12.
Rev Chil Pediatr ; 89(4): 432-440, 2018 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-30571815

RESUMO

Cancer is the second leading cause of death in the world, causing 8.8 million deaths in 2015 according to the World Health Organization (WHO). Risk factors for cancer include smoking and alcohol con sumption. In Chile, 33.6% of the population and 21.2% of young people smokes. Alcohol consump tion in the Chilean population is 74.5% and 12.2% in young people. Among the physiological factors that influence the development of cancer, the genetic factor plays a relevant role. It has been shown that the presence of genetic polymorphisms that alter the ability of the body to eliminate contami nants increase the risk of developing cancer. The same applies to polymorphisms that prevent DNA repair due to damage caused by environmental pollutants such as cigarette smoke. The objective of this review is to analyze the state of the art of the relationship between pharmacogenetics, smoking, and alcohol consumption as risk factors for the development of cancer. In conclusion, the results suggest that the presence of polymorphisms that alter the function of biotransformation enzymes phase I (CYP1A1, CYP1E1) and phase II (GST), as well as polymorphisms in DNA repair enzymes (ERCC1 / ERCC2), increase the risk of cancer induced by smoking and alcohol consumption. This association is important considering that smoking and drinking alcohol are highly prevalent among the Chilean population.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Predisposição Genética para Doença , Inativação Metabólica/genética , Neoplasias/etiologia , Fumar Tabaco/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/metabolismo , Marcadores Genéticos , Humanos , Neoplasias/metabolismo , Farmacogenética , Polimorfismo Genético , Fatores de Risco , Fumar Tabaco/genética , Fumar Tabaco/metabolismo
13.
Int J Mol Sci ; 18(6)2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-28545225

RESUMO

Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the appearance of complex characteristics that allow individuals to adapt to endemic environments, such as high altitude or extreme tropical weather. These genetic changes, most of them subtle and unexplored, could establish a mutational profile to develop new pharmacogenomic therapies specific for Latin American populations. In this review, we present the current status of research on somatic and germline alterations in Latin America compared to those found in Caucasian and Asian populations.


Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/genética , Farmacogenética/métodos , Povo Asiático , Fluxo Gênico , Humanos , América Latina , Polimorfismo de Nucleotídeo Único/genética , População Branca
14.
Rev Med Chil ; 145(4): 483-500, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28748996

RESUMO

Pharmacogenomics 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.


Assuntos
Esquema de Medicação , Farmacogenética , Polimorfismo Genético/genética , Humanos
15.
J Diagn Med Sonogr ; 32(1): 12-19, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26966729

RESUMO

The liver is one of the principal organs of our body involved in over 500 physiological functions related to metabolism, digestion, immunity, and storage of nutrients, which makes it an essential organ to preserve life. Given that there are a number of approaches to measure liver length through diagnostic 2D sonography, this work aims to determine the most accurate measurement of this organ. Cadaveric specimens (n = 21) were employed to assess measurements in midclavicular line (MCL) and midaxillary line (MAL). Each measurement was calculated in anteroposterior (AP) and craniocaudal (CC) planes. In addition, in situ measurements were obtained by accessing the organ through the anterior thoracoabdominal wall. Statistical differences were detected between MCL and MAL measurements (p < 0.05), a positive correlation between MAL CC and in situ anterior measurements were noted (r = 0.97). Liver size, as assessed through in situ measurements, varied as a funtion of BMI and waist circumference (p < 0.05). It is concluded that CC measurement of the RLL in MAL from the uppermost right hemi-diaphragm to the inferior tip of the right lobe through a horizontal line parallel to the anterior liver wall is the most accurate measurement of the organ by sonography.

16.
Pharmacol Res ; 101: 124-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26211952

RESUMO

We tested the influence of four polymorphisms and gene duplication in CYP2D6 on in vivo enzyme activity in a Chilean mestizo population in order to identify the most relevant genetic profiles that account for observed phenotypes in this ethnic group. CYP2D6*2 (2850C>T), *3 (2549A>del), *4 (1846G>A), *17 (1023C>T) and gene duplication were determined by PCR-RFLP or PCRL in a group of 321 healthy volunteers. Individuals with different variant alleles were phenotyped by determining debrisoquine 4-hydroxylase activity as a metabolic ratio (MR) using a validated HPLC assay. Minor allele frequencies were 0.41, 0.01, 0.12 and 0.00 for CYP2D6*2, *3, *4 and *17 variants, respectively, and the duplication frequency was 0.003. Genotype analysis correlated with phenotypes in 18 of 23 subjects (78.3%). 11 subjects were extensive metabolizers (EM), 8 were intermediate metabolizers (IM), 2 were poor metabolizers (PM) and 2 were ultra-rapid metabolizers (UM) which is fairly coincident with expected phenotypes metabolic ratios ranged from 0.11 to 126.41. The influence of CYP2D6*3 was particularly notable, although only heterozygote carriers were present in our population. Individuals homozygous for *4 were always PM. As expected, the only subject with gene duplication was UM. In conclusion, there was a clear effect of genotype on observed CYP2D6 activity. Classification of EM, PM and UM through genotyping was useful to characterize CYP2D6 phenotype in the Chilean mestizo population.


Assuntos
Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Adolescente , Adulto , Chile , Debrisoquina/metabolismo , Feminino , Duplicação Gênica , Frequência do Gene , Estudos de Associação Genética , Humanos , Indígenas Sul-Americanos/genética , Cinética , Masculino , Polimorfismo Genético , População Branca/genética , Adulto Jovem
17.
Acta Cardiol ; 70(5): 528-35, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26567812

RESUMO

OBJECTIVE: Among the genetic factors associated with cardiovascular disease (CVD), determining polymorphic genotypes could help to understand the appearance of the illness. Ethnic differences in these polymorphisms could explain population variability in susceptibility to CVD. The main goal of this research is to study the presence of more relevant genetic variants of ApoE, CETP, ACE, PAI-1, MTHFR, FII and FVL of the coagulation cascade, to describe the presence of cardiovascular-related variants in a mestizo group of the Chilean people. METHODS AND RESULTS: The studied population comprised 146 unrelated subjects from the general population, diagnosed as healthy, who were genotyped through conventional and/or real-time PCR. The allele frequencies for the Chilean population were: Apo E, ε2: 0.036, ε3: 0.875 and ε4: 0.089; CETP, B1: 0.51 and B2: 0.49; MTHFR, C: 0.52 and T: 0.48; ACE, I: 0.603 and D: 0.397; PAI-1, 4G: 0.381 and 5G: 0.619; FII, G: 0.97 and A: 0.03, and FV Leiden, G: 0.97 and A: 0.03. CONCLUSIONS: This study contributes to establish a first picture in the Chilean mestizo population about the frequencies of these variants, which could act as single or complementary risk factors to trigger CVD. The obtained allele frequencies show great differences in relation to other South American populations.


Assuntos
Doenças Cardiovasculares/genética , Indígenas Sul-Americanos/genética , Polimorfismo Genético , Adulto , Doenças Cardiovasculares/etnologia , Chile/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
18.
Toxicol Lett ; 398: 105-117, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901734

RESUMO

Inorganic arsenic species exist in the environment as a result of both natural sources, such as volcanic and geothermal activities, and geological formations, as well as anthropogenic activities, including smelting, exploration of fossil fuels, coal burning, mining, and the use of pesticides. These species deposit in water, rocks, soil, sediments, and the atmosphere. Arsenic-contaminated drinking water is a global public health issue because of its natural prevalence and toxicity. Therefore, chronic exposure to arsenic can have deleterious effect on humans, including cancer and other diseases. This work describes the mechanisms of environmental exposure to arsenic, molecular regulatory factors involved in its metabolism, genetic polymorphisms affecting individual susceptibility and the toxic effects of arsenic on human health (oxidative stress, DNA damage and cancer). We conclude that the role of single nucleotide variants affecting urinary excretion of arsenic metabolites are highly relevant and can be used as biomarkers of the intracellular retention rates of arsenic, showing new avenues of research in this field.

19.
Front Pharmacol ; 15: 1376638, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659583

RESUMO

Introduction: One of the primary obstacles faced by individuals with advanced colorectal cancer (CRC) is the potential development of acquired chemoresistance as the disease advances. Studies have indicated a direct association between elevated levels of miR-92a-3p and the progression, metastasis, and chemoresistance observed in CRC. We proposed that miR-92a-3p impairs FOLFOX (fluorouracil/oxaliplatin) chemotherapy response by upregulating the expression of chemoresistance biomarker genes through the activation of ß-catenin and epithelial-mesenchymal transition (EMT). These FOLFOX biomarker genes include the pyrimidine biosynthesis pathway genes dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and the genes encoding the DNA repair complexes subunits ERCC1 and ERCC2, and XRCC1. Methods: To assess this, we transfected SW480 and SW620 colon cancer cell lines with miR-92a-3p mimics and then quantified the expression of DPYD, TYMS, MTHFR, ERCC1, ERCC2, and XRCC1, the expression of EMT markers and transcription factors, and activation of ß-catenin. Results and discussion: Our results reveal that miR-92a-3p does not affect the expression of DPYD, TYMS, MTHFR, and ERCC1. Furthermore, even though miR-92a-3p affects ERCC2, XRCC1, E-cadherin, and ß-catenin mRNA levels, it has no influence on their protein expression. Conclusion: We found that miR-92a-3p does not upregulate the expression of proteins of DNA-repair pathways and other genes involved in FOLFOX chemotherapy resistance.

20.
Biomed Phys Eng Express ; 10(4)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38670074

RESUMO

Background. New applications of 3D printing have recently appeared in the fields of radiotherapy and radiology, but the knowledge of many radiological characteristics of the compounds involved is still limited. Therefore, studies are needed to improve our understanding about the transport and interaction of ionizing radiation in these materials.Purpose. The purpose of this study is to perform an analysis of the most important radiation interaction parameters in thermoplastic materials used in Fused Deposition Modeling 3D printing. Additionally, we propose improvements to bring their characteristics closer to those of water and use them as water substitutes in applications such as radiodiagnosis, external radiotherapy, and brachytherapy.Methods. We have calculated different magnitudes as mass linear attenuation, mass energy absorption coefficients, as well as stopping power and electronic density of several thermoplastic materials along with various compounds that have been used as water substitutes and in a new proposed blend. To perform these computations, we have used the XCOM and ESTAR databases from NIST and the EGSnrc code for Montecarlo simulations.Results. From the representation of the calculated interaction parameters, we have been able to establish relationships between their properties and the proportion of certain chemical elements. In addition, studying these same characteristics in different commercial solutions used as substitutes for water phantoms allows us to extrapolate improvements for these polymers.Conclusion. The radiological characteristics of the analyzed thermoplastic materials can be improved by adding some chemical elements with atomic numbers higher than oxygen and by using polyethylene in new blends.


Assuntos
Polímeros , Impressão Tridimensional , Água , Água/química , Polímeros/química , Método de Monte Carlo , Imagens de Fantasmas , Plásticos/química , Simulação por Computador , Humanos , Braquiterapia/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA