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1.
Lancet Infect Dis ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39116904

RESUMO

BACKGROUND: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. METHODS: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. FINDINGS: Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. INTERPRETATION: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. FUNDING: Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

2.
J Neurosci ; 44(23)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38631914

RESUMO

Foraging decisions involve assessing potential risks and prioritizing food sources, which can be challenging when confronted with changing and conflicting circumstances. A crucial aspect of this decision-making process is the ability to actively overcome defensive reactions to threats and focus on achieving specific goals. The ventral pallidum (VP) and basolateral amygdala (BLA) are two brain regions that play key roles in regulating behavior motivated by either rewards or threats. However, it is unclear whether these regions are necessary in decision-making processes involving competing motivational drives during conflict. Our aim was to investigate the requirements of the VP and BLA for foraging choices in conflicts involving overcoming defensive responses. Here, we used a novel foraging task and pharmacological techniques to inactivate either the VP or BLA or to disconnect these brain regions before conducting a conflict test in male rats. Our findings showed that BLA is necessary for making risky choices during conflicts, whereas VP is necessary for invigorating the drive to obtain food, regardless of the presence of conflict. Importantly, our research revealed that the connection between VP and BLA is critical in controlling risky food-seeking choices during conflict situations. This study provides a new perspective on the collaborative function of VP and BLA in driving behavior, aimed at achieving goals in the face of dangers.


Assuntos
Tonsila do Cerebelo , Prosencéfalo Basal , Recompensa , Animais , Masculino , Ratos , Prosencéfalo Basal/fisiologia , Tonsila do Cerebelo/fisiologia , Conflito Psicológico , Complexo Nuclear Basolateral da Amígdala/fisiologia , Assunção de Riscos , Ratos Long-Evans , Comportamento Alimentar/fisiologia , Medo/fisiologia
3.
N Engl J Med ; 390(5): 397-408, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38294972

RESUMO

BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).


Assuntos
Vacinas contra Dengue , Vírus da Dengue , Dengue , Vacinas Atenuadas , Adulto , Criança , Pré-Escolar , Humanos , Anticorpos Antivirais , Dengue/prevenção & controle , Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/uso terapêutico , Vírus da Dengue/imunologia , Método Duplo-Cego , Vacinação , Vacinas , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/uso terapêutico , Brasil , Eficácia de Vacinas , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Seguimentos
4.
Rev. cuba. reumatol ; 24(3)sept. 2022.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1530154

RESUMO

Introducción: La artrosis es una enfermedad reumatológica calificada y certificada en Chile a través de la Comisión de Medicina Preventiva y de Invalidez, conforme al marco de la Clasificación Internacional del Funcionamiento, la Discapacidad y la Salud; pero se desconoce cómo la discapacidad derivada de la artrosis se relaciona con indicadores de salud y sociodemográficos a nivel local. Objetivo: Investigar asociaciones entre variables relacionadas con la condición de salud, sociodemográficas y de calificación de discapacidad de las personas con diagnóstico de artrosis inscritas en el Registro Nacional de la Discapacidad en la Región de los Ríos, entre los años 2017-2019. Métodos: Estudio observacional, transversal, realizado de forma prospectiva y descriptiva en 427 personas con diagnóstico principal de artrosis. La muestra fue seleccionada de manera no probabilística desde la base de datos otorgada por la Comisión de Medicina Preventiva y de Invalidez de la región mencionada. Se utilizó el test de Chi-cuadrado y se consideró un resultado estadísticamente significativo si el valor de p < 0,05. Resultados: La muestra presentó predominantemente un grado leve de discapacidad y movilidad reducida, sexo femenino, 56-75 años de edad, casados, dueños de casa, con educación básica como máximo nivel alcanzado, residencia en zonas urbanas y adscritos al Fondo Nacional de Salud. Estas variables presentaron una asociación estadísticamente significativa con el grado de discapacidad. En variables vinculadas a la condición de salud, predominó la presencia de comorbilidades y la localización de artrosis en el miembro inferior. Hubo una asociación significativa entre el número de articulaciones afectadas y el grado de discapacidad. Conclusiones: Existe asociación entre los factores analizados y el grado de discapacidad. Los factores sociodemográficos presentaron una implicancia importante(AU)


Introduction: Osteoarthritis is a rheumatological disease that produces a significant impact in functionality on people who suffer from it, generating disability at different levels. This disability is measured and certified in Chile through the Commission for Preventive Medicine and Disability under criteria established in the framework of the International Classification of Functioning. However, it is unknown if sociodemographic indicators and the disability caused by osteoarthritis are related locally. Objective: To investigate associations between variables related to health condition, sociodemographic indicators, and disability index on people with a diagnosis of osteoarthritis registered in the National Disability Registry in the Los Rios Region between the years 2017 and 2019. Methods: Observational, cross-sectional study, carried out in a prospective and descriptive way in 427 people with osteoarthritis as a main diagnosis, registered in the National Disability Registry in the Los Rios Region. The sample was selected in a non-probabilistic way from the database provided by in the aforementioned region. The Chi-Squared test was used, and results were considered statistically significant if p < 0.05. Results: 53.9% of the participants presented a mild degree of disability and reduced mobility. 61.1% of the sample were female, predominantly between 56-75 years of age, married, homemakers, primary school as highest level of educational attainment, residence in urban areas, and registered with the National Health Fund. These variables presented show a statistically significant association with the degree of disability. As for those variables related to health condition, the presence of comorbidity and osteoarthritis located mainly in the lower limb predominated, and there was a significant association between the number of affected joints and the degree of disability. Conclusions: there is an association between the analyzed factors and the degree of disability, in which sociodemographic factors represented meaningful implications(AU)


Assuntos
Humanos , Osteoartrite/epidemiologia
5.
CES med ; 36(1): 17-29, ene.-abr. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1384216

RESUMO

Abstract Introduction: psoriasis is a systemic, inflammatory, and chronic disease with a global prevalence between 0.6-6.5 %. It is related to multiple comorbidities and generates a significant decrease in quality of life. Objective: to characterize sociodemographic, clinical, pharmacological, and quality of life variables in a population of patients with moderate-severe psoriasis. Methods: descriptive observational study the patients with a diagnosis of severe-moderate psoriasis treated in the Clínica Integral de Psoriasis-CLIPSO between May 2018 - June 2020. A collection format was designed for defined variables and a univariate analysis was performed. Results: 948 patients were identified with a median age of 50 years (IQR: 38-60) of which 51.0 % were women. 23.6 % were incidents with a median treatment time of 114 days (IQR: 98-127) and 73.9 % were prevalent with a median treatment time of 228 days (IQR: 160-371). The type of therapy used was mainly non-biological systemic and 90.9 % of the patients were adherent to the treatment. The clinical variables were similar for both groups and the most common phenotype was psoriasis vulgaris (57.1 %). The health-related quality of life in both groups was greater than 60 points and the affected dimensions were physical and psychological health. 27.3 % of the patients had comorbidities associated with cardiovascular risk and 44.7 % were overweight. Conclusion: knowing the sociodemographic, clinical, pharmacological, and quality of life characteristics of patients with moderate-severe psoriasis allows the identification of risk factors and comprehensive management of the disease.


Resumen Introducción: la psoriasis es una enfermedad sistémica, inflamatoria y crónica con una prevalencia global entre 0,6-6,5 %. Está relacionada con múltiples comorbilidades y genera una disminución significativa en la calidad de vida. Objetivo: caracterización sociodemográfica, clínica, farmacológica y calidad de vida de un grupo de pacientes con psoriasis moderada-severa. Métodos: estudio observacional descriptivo en pacientes con diagnóstico de psoriasis moderada-severa atendidos en la Clínica Integral de Psoriasis (CLIPSO) entre mayo 2018 y junio 2020. Se diseñó un formato para la recolección de las variables definidas y se realizó un análisis univariado. Resultados: se identificaron 948 pacientes con una mediana de edad de 50 años (RIC:38-60) de los cuales el 51 % eran mujeres. El 23,6 % eran incidentes, con una mediana en tiempo de tratamiento de 114 días (RIC:98-127) y 73,9 % eran prevalentes, con una mediana de tiempo de tratamiento de 228 días (RIC:160-371). El tipo de terapia utilizada fue principalmente sistémica no biológica y el 90,9 % de los pacientes eran adherentes al tratamiento. Las variables clínicas fueron similares en los incidentes y los prevalentes y el fenotipo más común fue psoriasis vulgar (57,1 %). La calidad de vida en ambos grupos fue mayor a 60 puntos y las dimensiones más afectadas en la calidad de vida fueron la salud física y la psicológica. El 27,3 % presentaban comorbilidades asociadas a riesgo cardiovascular y 44,7 % presentaban sobrepeso. Conclusión: conocer las características sociodemográficas, clínicas, farmacológicas y calidad de vida de los pacientes con psoriasis moderada-severa permite la identificación de factores de riesgo y un manejo integral de la enfermedad.

6.
Vaccine ; 38(28): 4405-4411, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32387012

RESUMO

BACKGROUND: Invasive meningococcal disease has a high mortality rate in individuals aged ≥56 years, but no vaccine is currently licensed in the USA for this age group. This study assessed the safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) compared with a meningococcal quadrivalent polysaccharide vaccine (MPSV4) in this age group. METHODS: This was a Phase III, modified double-blind, randomized, non-inferiority study (NCT02842866) across 35 clinical sites in the USA and Puerto Rico in individuals aged ≥56 years. A single dose of the MenACYW-TT (n = 451) or MPSV4 vaccine (n = 455) was administered on Day 0. A serum bactericidal assay with human (hSBA) and baby rabbit (rSBA) complement was used to measure antibodies against serogroups A, C, W, and Y test strains at baseline and Day 30. Safety data were collected up to six months post-vaccination. RESULTS: The seroresponse to MenACYW-TT was non-inferior to MPSV4 for each of the serogroups (A: 58.2% vs. 42.5%; C: 77.1% vs. 49.7%; W: 62.6% vs. 44.8%, Y: 74.4% vs. 43.4%, respectively). At Day 30, participants achieving hSBA titers ≥1:8 were higher for all serogroups after MenACYW-TT vs. MPSV4 (77.4-91.7 vs. 63.1-84.2%, respectively). No safety concerns were identified for either vaccine. CONCLUSION: MenACYW-TT was well-tolerated and immunogenic in ≥56-year-olds, offering the potential to replace MPSV4 in this age group.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Animais , Anticorpos Antibacterianos , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/efeitos adversos , Porto Rico , Coelhos , Toxoide Tetânico , Vacinas Conjugadas/efeitos adversos
7.
J Glob Antimicrob Resist ; 21: 285-290, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32315776

RESUMO

OBJECTIVE: This investigation aimed to detect coincidences in the antimicrobial resistance genes (ARG) profiles between members of a group living in a household and to compare them between other groups in order to establish if an exchange of ARG occurs and if dental plaque microbiota can be considered as a source and reservoir of ARG that can be shared between humans and pets. METHODS: One hundred sixty dental plaque samples were obtained from four groups: Shelter dogs group (n=20), adult pet owners and dogs group (AD group, n=40), adult pet owners, children and dogs group (ACD group, n=60), and adult non-pet owners and children group (AC group, n=40). DNA was obtained, and specific primers with polymerase chain reaction for ARG detection were used. RESULTS: The AD group exhibited the most coincidences in their ARG profiles, 14 (70%) of the 20 profiles coincided in 100% followed by the ACD group with 9 (45%) coincidences. While the AC group was the less coincident group, only 7 (35%) of the 20 profiles coincided. tetM was the most prevalent with 53.1%, followed by tetQ with 52.5% and cfxA with 51.2%, while the less prevalent were tetW with 31.8%, blaTEM-1 with 27.5%, and ermC with 18.7%. CONCLUSION: Dental plaque microbiota can be considered as a source and reservoir of ARG that can be shared between humans and dogs living in a household. The dogs seem to play an important role in the transference of ARG, and the children appear to be the most affected by carrying the most significant number of ARG.


Assuntos
Placa Dentária , Microbiota , Animais , Antibacterianos/farmacologia , Cães , Farmacorresistência Bacteriana , Animais de Estimação
8.
Plant Dis ; 104(1): 211-221, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765279

RESUMO

Phytophthora infestans is the causal agent of late blight disease of potatoes and tomatoes. This disease causes devastating economic losses each year, and control is mainly achieved by the use of fungicides. Unfortunately, populations of P. infestans resistant to fungicides have been documented. Furthermore, studies have reported that sensitive isolates to the phenylamide fungicide, mefenoxam, become less sensitive in vitro after a single passage through sublethal concentrations of fungicide-amended medium. The first objective of this study was to investigate if isolates of P. infestans are capable of acquiring resistance to two additional systemic fungicides, fluopicolide (benzamide) and cymoxanil (cyanoacetamide-oxime). In contrast to the situation with mefenoxam, exposure of isolates to sublethal concentrations of fluopicolide and cymoxanil did not induce reduced sensitivity to these two fungicides. The second objective was to assess if reduced sensitivity to mefenoxam could occur in naturally sensitive isolates of other Phytophthora species and of Phytopythium sp., another oomycete plant pathogen. All Phytophthora spp. assessed (P. infestans, P. betacei, and P. pseudocryptogea) as well as Phytopythium sp. acquired resistance to mefenoxam after previous exposure through medium containing 1 µg ml-1 of mefenoxam. Interestingly, isolate 66 of Phytopythium sp. and the isolate of P. pseudocryptogea tested do not seem to be acquiring resistance to mefenoxam after exposure to medium containing 5 µg ml-1 of this fungicide. The tested isolates of P. palmivora and P. cinnamomi were extremely sensitive to mefenoxam, and thus it was not possible to perform a second transfer to access acquisition of resistance to this fungicide.


Assuntos
Alanina/análogos & derivados , Farmacorresistência Fúngica , Phytophthora infestans , Alanina/farmacologia , Fungicidas Industriais/farmacologia , Phytophthora infestans/efeitos dos fármacos , Solanum tuberosum/microbiologia
9.
CES med ; 33(2): 100-110, mayo-ago. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1055536

RESUMO

Resumen Introducción: la exposición dietaria a la aflatoxina es un factor de riesgo para carcinoma hepatocelular, el cáncer primario de hígado más frecuente. Esta asociación se estableció gracias a la evidencia in vitro e in vivo de la relación entre la exposición a la aflatoxina B1 y la transversión G→T en el codón 249 del gen TP53, así como evidencia de la sinergia entre la aflatoxina y la infección crónica por virus de la hepatitis B. Métodos: se determinó la frecuencia de la mutación R249S del gen TP53 en 30 pacientes con diagnóstico de cirrosis y/o carcinoma hepatocelular quienes fueron sometidos a trasplante hepático en un hospital en Medellín, Colombia. Se extrajo ADN a partir de las muestras de explante hepático, se amplificó el fragmento de interés y se detectó la mutación por polimorfismos de longitud de fragmentos de restricción. Resultados: se encontró la mutación R249S en una de las 30 muestras analizadas (3,33 %) y se determinó, por medio de marcadores serológicos, infección por el virus de la hepatitis B en dos casos (6,67 %). No se encontró simultáneamente la mutación y la presencia de los marcadores de infección por virus de la hepatitis B. Conclusión: los resultados sugieren una baja exposición dietaria con aflatoxina B1 en la población de estudio. Sin embargo, es importante tener en cuenta la regulación de los límites permisibles de aflatoxina B1 y la inclusión en el diagnóstico diferencial de carcinoma hepatocelular, dada la heterogeneidad de las condiciones de la población en diferentes regiones del país.


Abstract Introduction: The dietary exposure to aflatoxin is a risk factor of hepatocellular carcinoma, the most frequent primary liver cancer. This risk factor was identified after in vivo and in vitro evidence of the relation between exposure to aflatoxin B1 and transversion G → T at 249 codon of the TP53 gene; as well as evidence of the synergy between hepatitis B virus chronic infection. Methods: the frequency of the R249S mutation of the TP53 gene was determined in 30 cases of cirrhosis and/or hepatocellular carcinoma, with liver transplantation in the hepatology unit of a hospital in Medellín, Colombia. DNA was extracted from the liver explant samples; the sequence of interest was amplified, and the mutation was detected by restriction fragment length polymorphisms. Results: the R249S mutation was found in 1 of the 30 samples analyzed (3.33 %); and hepatitis B virus infection was detected by serological markers in 2 of the 30 cases (6.67 %). We did not find the mutation and the presence of hepatitis B virus infection markers at the same time in any of the samples. Conclusion: The results suggest a low dietary exposure with aflatoxin B1 in the study population. However, it is important to take into consideration the regulation of the permissible limits of aflatoxin B1 and the inclusion in the differential diagnosis of hepatocellular carcinoma, given the heterogeneity of the conditions of the population in different regions of the country.

10.
Biomédica (Bogotá) ; 38(4): 555-568, oct.-dic. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-983966

RESUMO

Introducción. Uno de los principales factores de riesgo del carcinoma hepatocelular es el consumo crónico de alcohol. En estudios en diferentes poblaciones, se sugiere que las variantes genéticas de las enzimas que participan en el metabolismo del alcohol, como la alcohol deshidrogenasa (ADH) y la citocromo P450 (CYP2E1), estarían asociadas con riesgo de enfermedades hepáticas terminales. Objetivo. Identificar y caracterizar las variantes alélicas de los genes ADH1B, ADH1C y CYP2E1 en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular. Materiales y métodos. Se incluyeron muestras de pacientes atendidos entre el 2005 y el 2007, y entre el 2014 y el 2016, en la unidad de hepatología de un hospital de Medellín. La genotipificación de las muestras se hizo mediante reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) con análisis de los polimorfismos en la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Los resultados se compararon con los de dos grupos de control y con lo reportado en la base de datos del 1000 Genomes Project. Resultados. Se recolectaron 97 muestras de pacientes con diagnóstico de cirrosis y carcinoma hepatocelular. Los dos factores de riesgo más frecuentes fueron el consumo crónico de alcohol (18,6 %) y las colangiopatías (17,5 %). Los genotipos más frecuentes en la población de estudio fueron el ADH1B*1/1 (82 %), el ADH1C*1/1 (59 %) y el CYP2E1*C/C (84 %). Conclusiones. En este primer estudio de los polimorfismos en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular, los genotipos más frecuentes fueron el ADH1B*1/1, el ADH1C*1/1 y el CYP2E1*C/C. No se observaron diferencias estadísticamente significativas en la frecuencia de los genotipos entre los casos y los controles. Se requieren estudios adicionales en población colombiana para evaluar el riesgo de la enfermedad hepática terminal por consumo crónico de alcohol y la asociación con los polimorfismos.


Introduction: One of the most important risk factors for hepatocellular carcinoma (HCC) is alcohol consumption: Studies in different populations suggest that the risk of liver disease could be associated with genetic variants of the enzymes involved in alcohol metabolism, such as alcohol dehydrogenase (ADH) and cytochrome P450 CYP2E1. Objective: To identify and characterize the allelic variants of ADH1B, ADH1C and CYP2E1 genes in Colombian patients with cirrhosis and/or HCC. Materials and methods: We included samples from patients attending the hepatology unit between 2005-2007 and 2014-2016 of a hospital in Medellin. Samples were genotyped using PCR-RFLP. We compared the results with two control groups and the 1000 Genomes Project database. Results: We collected 97 samples from patients with a diagnosis of cirrhosis and/or HCC. The two main risk factors were chronic alcohol consumption (18.6%) and cholangiopathies (17.5%). The most frequent genotypes in the study population were ADH1B*1/1 (82%), ADH1C*1/1 (59%), and CYP2E1*C/C (84%). Conclusions: This first study of polymorphisms in Colombian patients diagnosed with cirrhosis and/or HCC showed genotypes ADH1B*1/1, ADH1C*1/1 and CYP2E1*C/C as the most frequent. We found no significant differences in the genotype frequency between cases and controls. Further studies are necessary to explore the association between polymorphisms and the risk of end-stage liver disease from alcohol consumption.


Assuntos
Álcool Desidrogenase , Citocromo P-450 CYP2E1 , Carcinoma Hepatocelular/etiologia , Alelos , Genótipo , Cirrose Hepática/etiologia
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