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Progressive retinal atrophy (PRA) is a term used in veterinary medicine to describe inherited and progressive retinal diseases characterized by progressive retinal degeneration and loss of vision. In the Golden Retriever (GR) breed, the mutations associated with PRA have an autosomal recessive inheritance pattern. This study aimed to verify the allele frequencies of PRA1, PRA2, and PRA-prcd in the GR breed in Brazil. A total of 121 GR DNA samples (n = 66 females and n = 55 males) were analyzed. All animals assessed in this study were identified as wild-type (121/121 animals; 100%) for PRA1 and PRA2 mutations; therefore, no carrier or homozygous animals were identified in this population. For the PRA-prcd mutation, 118 animals (118/121 animals; 97.52%) were wild-type. Three animals were genotyped as heterozygous for PRA-prcd (3/121 animals; 2.47%), demonstrating that this mutation is still present in some bloodlines and animals in Brazil, even with a rare prevalence. Five animals (5/121 animals, 4.2%) had a previous eye disease, which was diagnosed by a veterinarian as entropion (2 animals), keratoconjunctivitis sicca (1 animal), corneal ulcer (1 animal), and bilateral blindness (1 animal). This dog with bilateral blindness was identified as wild type homozygous for three mutations assessed in this study; therefore, blindness was not associated with the investigated mutations. In addition, the vast majority (98.3%) of Brazilian breeders assessed in this study were unaware of these mutations as a cause of blindness in the Golden Retriever. Therefore, the present study will serve to disseminate knowledge about PRA and its genetic etiologies, as well as to support future studies with other Brazilian GR populations.
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ABSTRACT: Pancreatic cysts are rare in both humans and animals. They are defined as an enclosed structure externally surrounded by a capsule, internally coated with a cuboidal epithelium and filled with liquid or semi-solid content. This case described the clinical and pathological characteristics of a pancreatic cyst in a feline. A mixed breed cat with a history of recurrent vomiting was attended. Physical examination revealed pain on abdominal palpation. Abdominal ultrasonography showed a cystic, anechoic structure with well-defined edges located in the left cranial abdomen and in close contact with the duodenum and pancreas. Partial pancreatectomy was performed. Microscopically, the structure was surrounded by fibrous material, coated with cuboidal to columnar epithelium, and containing eosinophilic material. Although, pancreatic cyst is rare in animals, they should be included in the differential diagnosis of causes of vomiting in young cats.
RESUMO: Os cistos epiteliais pancreáticos são raros em humanos e animais, e são definidos como estruturas encapsuladas rodeadas por epitélio cuboidal, preenchido por substância líquida. O objetivo desse estudo foi descrever as características clínico-patológicas de um cisto pancreático verdadeiro em um felino. Foi atendido uma gata sem raça definida com histórico de vômitos recorrentes. No exame físico o animal apresentou dor à palpação abdominal. Na ultrassonografia abdominal, evidenciou-se a presença de uma estrutura cística, anecóica e com bordos bem definidos localizado no abdome cranial esquerdo, em contato com o duodeno e o pâncreas. Foi realizada pancreatectomia parcial. No exame microscópico observou-se estrutura encapsulada, circundado por material fibroso, revestido por epitélio cuboidal a colunar, contendo material eosinofílico. Embora os cistos pancreáticos verdadeiros sejam raros nos animais, eles devem ser incluídos no diagnóstico diferencial de doenças que cursam com vômitos nos gatos.
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It is well established that healthy aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD) are associated with substantial declines in episodic memory. However, there is still debate about the roles of GPX1 and GPX4 polymorphisms. The aim of this study was to investigate the association of rs1050450 and rs713041 polymorphisms with memory. This research was composed of a cross-sectional study (334 subjects) and a case-control study (108 healthy controls and 103 with AD-NINCDS/ARDA, DSM-IV-TR criteria). For the association of the genetic polymorphisms with memory or cognitive loss, the phenotypes were analyzed as follows: 1) each memory as a quantitative trait; 2) presence of deficit on a specific memory; 3) presence of MCI; 4) presence of AD. To assess verbal learning and the ability to store new information, we used the Rey Verbal Learning Test. Scores were recorded as a function of age as in the WMS-R testing battery. DNA was obtained from whole blood, and genotypes for GPX1 (rs1050450) and GPX4 (rs713041) were detected by allelic discrimination assay using TaqMan® MGB probes on a real-time PCR system. GPX1 TT homozygotes had lower long-term visual memory scores than CC/CT group (-0.28⯱â¯1.03 vs. 0.13⯱â¯1.03, respectively, pâ¯=â¯0.017). For the GPX4 rs713041, the frequency of the TT genotype was higher in the group with normal scores than in the group with long-term visual memory deficits (pâ¯=â¯0.025). In a multivariate logistic regression, GPX1 CC homozygotes had a 2.85 higher chance of developing AD (ORâ¯=â¯2.85, CI95%â¯=â¯1.04-7.78, pâ¯=â¯0.041) in comparison to the reference genotype. No significant differences were observed regarding the MCI group between genetic variants. This study is one of the first to show that polymorphisms in GPX1 and GPX4 are significantly associated with episodic memory and AD in a South Brazilian population.
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Enfermedad de Alzheimer/genética , Disfunción Cognitiva/genética , Glutatión Peroxidasa/genética , Polimorfismo Genético/genética , Adulto , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/complicaciones , Estudios Transversales , Femenino , Genotipo , Humanos , Masculino , Memoria Episódica , Persona de Mediana Edad , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Aprendizaje Verbal , Glutatión Peroxidasa GPX1RESUMEN
Abstract Objective: To analyze the memory performance of participants aged 60 years and older with and without depressive symptoms. Methods: 199 participants were assessed using the Beck Depressio. In ventory (BDI) with a cut-off point of 20 for depression. Of these, 22 met the criteria for depression group; the remaining participants were allocated to the non-depression group. The Rey Auditory-Verbal Learning Test (RAVLT) was used to assess verbal learning, figures I and II of the Visual Reproduction subtest of the Wechsler Memory Scale Revised (WMS-R) was used to evaluate immediate and delayed visual memory, and the Logical Memory subtests I and II of WMS-R were used to test verbal memory. Results: The average scores for verbal learning in the depression group were significantly lower than those in the non-depression group (p = .001). There were no group differences on visual and logical memory I and II scales. Conclusion: Depressive symptoms affect information retention and verbal learning in the elderly. However, they had no effect on visual and logical memory processing in this sample. The results suggest that, in addition to age-related cognitive decline, depression impairs memory performance considerably.
Resumo Objetivo: analisar o desempenho de memória de participantes com 60 anos ou mais de idade, apresentando ou não sintomas de depressão. Métodos: 199 participantes foram examinados através d. In ventário de Depressão de Beck (BDI) com ponto de corte em 20 pontos para depressão. 22 participantes atingiram o critério para inclusão no grupo de depressão e o restante foi alocado no grupo sem depressão. Os testes utilizados foram: Rey Auditory-Verbal Learning Test (RAVLT) para avaliar aprendizagem verbal, teste de reprodução de figuras I e II da Escala Wechsler Revisada (WMS-R) para memória visual imediata e duradoura e teste de memória lógica I e II da WMS-R para memória verbal. Resultados: os escores médios para aprendizagem verbal no grupo com depressão foram significativamente mais baixos do que no grupo sem depressão (p= 0,001). Não ocorreram diferenças significativas entre os grupos nas escalas para memória visual ou lógica I e II. Conclusões: sintomas de depressão afetam a retenção de informação e a aprendizagem verbal em idosos. Entretanto, não parecem afetar o processamento das memórias visual e lógica. Os resultados sugerem que, além do declínio cognitivo devido ao envelhecimento, a presença de depressão afeta e empobrece o desempenho de memória.
Resumen Objectivo: Analizar el rendimiento de la memoria de participantes con mas de 60 anos con sintomas de depresion. Metodos: 199 participantes fueron examinados a traves de. In ventario de Depresion de Beck (BDI), tomando en consideracion acima de 20 puntos para la depresion. 22 participantes alcanzaron el criterio de inclusion en el grupo de depresion y lo restante fue colocado en el grupo sin depresion. Las pruebas utilizadas fueron: Rey Auditory-Verbal Learning Test para evaluar el aprendizaje verbal; Prueba de Reproduccion de Figuras I y II de Wechsler Memory Scale (WMS-R) para memoria inmediata y duradera, memoria visual y logica de ensayo I y II de la WMS-R para memoria verbal. Resultados: La aprendizaje verbal en el grupo con depresion fue abajo que en el grupo sin depresion (p = .001). No hubo diferencias significativas entre los grupos en las escalas para memoria I y II visual y logica. Conclusiones: La depresion afecta la retencion de informacion y aprendizaje verbal en los ancianos pero no parece afectar el procesamiento de los recuerdos visuales y logicos. Los resultados sugieren que, ademas de deterioro cognitivo debido al envejecimiento, afecta a la presencia de depresion y el rendimiento de la memoria se vuelve pobre.
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AIMS: To evaluate oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin, relating these values to its side effects, plasma levels, glycemic control, diabetic complications, lipid profile, and the influence of pharmacotherapeutic follow-up. METHODS: Patients with type 2 diabetes mellitus, on metformin and in pharmacotherapeutic follow-up for four months, were evaluated. The pharmacotherapeutic follow-up consisted in providing information and answering patients' questions about medication and disease. In addition, administration times, dosages, and presence or absence of side effects related to the use of metformin were verified. Glycemic and lipid profile, oxidative stress (superoxide dismutase and malondialdehyde) and plasma metformin were evaluated. Pearson's correlation and Spearman's correlation were performed to evaluate the relationship between the variables at the beginning of the study. The independent t-test and Mann-Whitney U test were used to assess the difference between the groups with and without diabetic complications. The range of values between the beginning and end of the study was evaluated using Student's t-test or Wilcoxon U test. The significance level was set at 5%. RESULTS: The initial sample consisted of 49 patients aged 59±9 years with a body mass index of 29.8±5.1 kg/m2 , who have had diabetes for a median time of 36 months (interquartile range of 1-240) and have been on metformin for a median time of 36 months (interquartile range of 1-180). Twenty-five patients left the study between the second and fourth meetings. Malondialdehyde levels differed between before and after pharmacotherapeutic follow-up, being positively correlated with blood glucose, glycohemoglobin, and triglyceride level, and negatively correlated with metformin and superoxide dismutase. Blood glucose, glycohemoglobin, and malondialdehyde levels increased, whereas metformin levels decreased in the group with diabetic complications, and there was a correlation between malondialdehyde and the number of diabetic complications per patient. CONCLUSIONS: In this sample of patients with type 2 diabetes mellitus treated with metformin, oxidative stress was more pronounced in those with poor glycemic control and diabetic complications.
OBJETIVOS: Avaliar parâmetros de estresse oxidativo em pacientes com diabetes mellitus tipo 2 em uso de metformina, relacionando estes valores a seus efeitos adversos, níveis plasmáticos, controle glicêmico, complicações diabéticas, perfil lipídico, e a influência do acompanhamento farmacoterapêutico. MÉTODOS: Foram avaliados pacientes com diabetes mellitus tipo 2, em uso de metformina, em acompanhamento farmacoterapêutico por quatro meses. O acompanhamento farmacoterapêutico consistiu na prestação de informações e no esclarecimento de dúvidas dos pacientes sobre a medicação e a doença. Além disto, foram verificados os horários, as doses e a presença ou não de efeitos adversos relacionados ao uso de metformina. Foram avaliados perfil glicêmico e lipídico, estresse oxidativo (superóxido dismutase e malondialdeído) e metformina plasmática. Foram realizados os testes de correlação de Pearson e de Spearman para avaliar as relações entre as variáveis no início do estudo. Para testar a diferença entre os grupos com e sem complicações diabéticas, foram utilizados o t-teste independente ou o teste U de MannWhitney. A gama de valores entre o início e o final do estudo foi avaliada utilizando o teste t de Student ou o teste de Wilcoxon U. Foi adotado um nível de significância de 5%. RESULTADOS: A amostra inicial foi composta por 49 pacientes com idade de 59±9 anos e índice de massa corporal de 29,8±5,1 kg/m2 , com diabetes por uma mediana de tempo de 36 (intervalo interquartil 1-240) meses e em uso de metformina há uma mediana de 36 (intervalo interquartil 1-180) meses. Vinte e cinco pacientes deixaram o estudo entre a segunda e a quarta reunião. Os níveis de malondialdeído diferiram entre antes e após o acompanhamento farmacoterapêutico, correlacionando-se positivamente com glicemia, glicohemoglobina e triglicerídeos e negativamente com metformina e superóxido dismutase. Encontrou-se elevação da glicemia, glicohemoglobina e malondialdeído, e diminuição da metformina no grupo com complicações diabéticas, e foi identificada correlação entre malondialdeído e o número de complicações diabéticas por paciente. CONCLUSÕES: Nesta amostra de pacientes com diabetes mellitus tipo 2 em tratamento com metformina, o estresse oxidativo foi mais pronunciado nos que apresentavam pior controle glicêmico e complicações diabéticas.
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Estrés Oxidativo , Diabetes Mellitus Tipo 2 , Metformina , Superóxido Dismutasa , Índice Glucémico , Complicaciones de la Diabetes , Malondialdehído , Metformina/efectos adversos , Metformina/farmacologíaRESUMEN
Alzheimer's disease (AD) is a complex and multifactorial disease with the contribution of several genes and polymorphisms to its development. Among these genes, the APOEε4 is the best known risk factor for AD. Methylation is associated with APOE expression and AD development. Recently, we found an association of the TGG haplotype in the DNMT3B gene, one of the catalyst enzyme for methylation, with AD. Therefore, the objective of the study was to investigate whether APOEε4 and TGG haplotype have an synergistic effect on AD. The sample was composed of 212 Caucasian individuals (108 healthy controls and 104 with AD by NINCDS-ADRDA and DSM-IV-TR criteria) from southern Brazil. The genetic analyses were performed by real time PCR for TaqMan(®) assay. Multivariate logistic regression was performed categorizing groups according to presence of APOEε4 and/or TGG haplotype as an independent variable for outcome AD. The presence of TGG haplotype plus the allele APOEε4 were strongly associated with AD [OR 11.13; 95 % CI (4.25-29.16); P < 0.001]. This association had a higher risk than each risk factor alone. We found a strong association of the interaction of DNMT3B gene with the APOEε4 in this sample of AD patients. The presence of TGG haplotype and APOEε4 significantly increased the risk of developing the disease, showing an synergistic effect.
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Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Epistasis Genética , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Factores de Riesgo , ADN Metiltransferasa 3BRESUMEN
Recent research suggests that crack cocaine use alters systemic biochemical markers, like oxidative damage and inflammation markers, but very few studies have assessed the potential effects of crack cocaine at the cellular level. We assessed genome instability by means of the comet assay and the cytokinesis-block micronucleus technique in crack cocaine users at the time of admission to a rehabilitation clinic and at two times after the beginning of withdrawal. Thirty one active users of crack cocaine and forty control subjects were evaluated. Comparison between controls and crack cocaine users at the first analysis showed significant differences in the rates of DNA damage (p = 0.037). The frequency of micronuclei (MN) (p < 0.001) and nuclear buds (NBUDs) (p < 0.001) was increased, but not the frequency of nucleoplasmic bridges (NPBs) (p = 0.089). DNA damage decreased only after the end of treatment (p < 0.001). Micronuclei frequency did not decrease after treatment, and nuclear buds increased substantially. The results of this study reveal the genotoxic and mutagenic effects of crack cocaine use in human lymphocytes and pave the way for further research on cellular responses and the possible consequences of DNA damage, such as induction of irreversible neurological disease and cancer.
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Trastornos Relacionados con Cocaína , Cocaína Crack/toxicidad , Inestabilidad Genómica/efectos de los fármacos , Linfocitos/efectos de los fármacos , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Adolescente , Adulto , Brasil , Núcleo Celular/efectos de los fármacos , Núcleo Celular/genética , Ensayo Cometa , Daño del ADN/efectos de los fármacos , Humanos , Linfocitos/citología , Masculino , Pruebas de Micronúcleos , Persona de Mediana Edad , Membrana Nuclear/efectos de los fármacos , Membrana Nuclear/genéticaRESUMEN
Because of their numerous roles in several biological processes, zinc and selenium are the most commonly studied micronutrients in the elderly. Therefore, we hypothesized that the polymorphisms in the genes that are responsible for the transport of zinc and selenium may have a genotype-dependent effect on the serum concentration of these micronutrients. The objective of this study was to determine the effects of solute carrier family 30 member 3 (SLC30A3) and 15-kd selenoprotein (SEP15) polymorphisms on zinc and selenium concentrations, respectively, in the serum. This cross-sectional study included 110 individuals who were aged 50 years or older. Serum micronutrient concentrations were determined by flame atomic absorption spectrophotometry (for zinc) and by atomic absorption spectrophotometry with a graphite furnace (for selenium). The single-nucleotide polymorphisms, rs73924411 and rs11126936 of the SLC30A3 gene and rs5859, rs5854, and rs561104 of the SEP15 gene, were examined by real-time polymerase chain reaction. Regarding rs11126936, the serum zinc concentration was lower in CC homozygotes (0.75 ± 0.31 mg/L) than in A carriers (0.89 ± 0.28 mg/L, P = .016). Concerning rs561104, the serum selenium concentration was higher in CC homozygotes (5.65 ± 1.11 µg/dL) compared with T carriers (4.88 ± 1.25 µg/dL, P = .044). Our results demonstrate the influence of SLC30A3 and SEP15 gene polymorphisms on the serum concentrations of zinc and selenium, respectively. The effects of these associations should be further investigated to help elucidate the modes of action of trace elements and to identify biomarkers, which could ultimately define the optimal intake of these micronutrients at the molecular level. More research must be performed before the roles of these polymorphisms in the serum concentrations of zinc and selenium can be fully understood.
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Proteínas de Transporte de Catión/genética , Genotipo , Polimorfismo de Nucleótido Simple , Selenio/sangre , Selenoproteínas/genética , Oligoelementos/sangre , Zinc/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional/genética , Selenio/deficiencia , Oligoelementos/deficiencia , Zinc/deficienciaRESUMEN
Epigenetic mechanisms have been implicated in syndromes associated with neuropsychiatric disorders, but little is known about the role of epigenetics in Alzheimer's disease (AD). DNA methylation, one of the main epigenetic mechanisms, is a complex process carried out by specific enzymes, such as DNMT1 and DNMT3B. This study aimed to investigate the association between DNMT1 and DNMT3B polymorphisms and AD. Two hundred and ten elderly subjects (108 healthy controls and 102 with AD-NINCDS/ARDA, DSM-IV-TR criteria) were assessed. DNA was obtained from whole blood, and genotypes were detected by an allelic discrimination assay using TaqMan(®) MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560, rs759920 (DNMT1) and rs998382, rs2424913, rs2424932 (DNMT3B). For both genes, the polymorphisms were in strong linkage disequilibrium. Carriers of the DNMT3B TGG haplotype were associated with AD (OR=3.03, 95% CI 1.63 to 5.63, P<0.001). No significant difference between AD and the control group were observed for DNMT1 polymorphisms. This study is one of the first describing a significant association between DNMT3B polymorphisms and AD. This enzyme, which is responsible for methylation in a general way, may be involved in AD.
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Enfermedad de Alzheimer/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Metilasas de Modificación del ADN/genética , Haplotipos/genética , Anciano , Estudios de Casos y Controles , ADN (Citosina-5-)-Metiltransferasa 1 , Epigénesis Genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Isoenzimas/genética , Masculino , Pruebas Neuropsicológicas , Fenotipo , Polimorfismo Genético/genética , ADN Metiltransferasa 3BRESUMEN
BACKGROUND: Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer's disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations. METHODS: To confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies. RESULTS: Seventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ(2)â=â119.46, ORâ=â2.79, 95% CIâ=â2.31-3.36, P<0.01). CONCLUSIONS: The APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD.
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Enfermedad de Alzheimer/genética , Apolipoproteína C-I/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Negro o Afroamericano/genética , Anciano , Enfermedad de Alzheimer/etnología , Apolipoproteína E4/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Genotipo , Hispánicos o Latinos/genética , Humanos , Modelos Lineales , Metaanálisis como Asunto , Factores de Riesgo , Población Blanca/genéticaRESUMEN
Memory deficits are common during aging, but little is known about the impact of environmental and genetic variables on memory. The genes SLC30A3 and SEP15 are, respectively, responsible for transporting zinc and selenium, micronutrients that are neuroprotective agents. The aim of this study was to investigate the effect of nutrigenetic interactions on the memory scores of volunteers more than 50 years old. For this cross-sectional study, 240 individuals were enrolled. Micronutrient dosage was determined using atomic absorption spectrophotometry. The SNPs rs5859, rs5854, and rs561104 in SEP15 and rs73924411 and rs11126936 in SLC30A3 were determined by real-time PCR. The evaluations of verbal and visual memory were performed using the Weschler Memory Scale-revised and the Rey's verbal learning test. A gene versus nutrient interaction was observed for SLC30A3 rs73924411 and zinc concentration. Carriers of the T allele had higher scores for short-term and long-term verbal memories than CC homozygotes only when zinc serum concentration was below the recommended level (p value for the interaction for short-term verbal memory = 0.011, p value for the interaction for long-term verbal memory = 0.039). For SEP15, C carriers of the rs5845 SNP allele had higher verbal learning memory scores than TT homozygotes (0.13 ± 1.13 vs. -1.10 ± 1.20, p = 0.034). Our results suggest the influence of genetic polymorphisms on memory score and identify gene versus nutrient interactions between zinc serum concentration and memory score.
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The hyperglycaemia seen in type 2 diabetes mellitus (DM2) is associated with increased oxidative stress and production of reactive oxygen species, both of which are factors that can provoke DNA damage. Notwithstanding, other factors, including medications and individual susceptibility, can also induce this type of DNA lesion. The objective of this study was, therefore, to investigate the influence of glycaemic control, oral antidiabetic drugs (metformin and glibenclamide) and polymorphisms of the XRCC1 and XRCC3 genes on the frequency of DNA damage in DM2 patients, which was accessed by the cytokinesis-block micronucleus cytome and the comet assays on the ex vivo mitogenically stimulated lymphocytes. The 53 people recruited to take part in the study were already on treatment with metformin and were followed for 5 months. Ten of these patients were put on combined treatment with the addition of glibenclamide. It was observed that the greater the plasma metformin concentration, the lower the frequency of micronuclei (MN) in the sample total (P = 0.009) and also that the subset of patients using combined treatment including glibenclamide had a significantly higher MN rate 90 days after starting combined treatment (P = 0.024). In the subset who only took metformin, the rate of MN was significantly higher among carriers of the 399Gln allele on the XRCC1 gene (P = 0.008). In addition, homozygotes for the 241Thr allele exhibited a significant increase in MN in the combined treatment group (P = 0.008). Our results suggest that different combinations of oral antidiabetic drugs and polymorphisms on genes involved in the DNA damage repair system could influence the frequency of this type of chromosome lesion, which can be a useful biomarker for assessing the risk of developing cancer.
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Daño del ADN/efectos de los fármacos , Proteínas de Unión al ADN/genética , Diabetes Mellitus Tipo 2/genética , Hipoglucemiantes/uso terapéutico , Administración Oral , Adulto , Anciano , Ensayo Cometa , Estudios Transversales , Daño del ADN/genética , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Gliburida/administración & dosificación , Gliburida/sangre , Gliburida/uso terapéutico , Humanos , Hipoglucemiantes/administración & dosificación , Masculino , Metformina/sangre , Metformina/farmacología , Metformina/uso terapéutico , Pruebas de Micronúcleos , Persona de Mediana Edad , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
OBJECTIVE: A previous study by our research group evaluated the levels of DNA damage using the comet assay in hemodialysis patients with type 2 diabetes mellitus. The same blood samples were also evaluated using the cytochalasin B micronucleus assay. A comparison of the results of the two assays is presented here. METHODS: Whole blood samples were collected from 22 type 2 diabetes mellitus patients on hemodialysis and from 22 control subjects. Samples were collected from patients early in the morning on Mondays, before the first weekly hemodialysis session. The cytokinesis-block micronucleus assay (CBMN) was used to evaluate genomic instability. RESULTS: The frequencies of micronuclei and nuclear buds were higher in patients than in controls (p-value = 0.001 and p-value < 0.001, respectively). There was a correlation between the frequency of micronuclei and DNA damage with the results of the comet assay (p-value < 0.001). The difference in the frequency of micronuclei and nuclear buds between patients and controls was more pronounced in the group with higher median comet values than in the group with lower comet values. CONCLUSION: Our results suggest that the increased rates of DNA damage as measured by the comet assay and influenced by the weekly routine therapy of these patients has a mutagenic effect, thereby increasing the risk of cancer in this group.
RESUMEN
Objetivo - Avaliar se polimorfismos nos genes CETP (proteína transferidora de ésteres de colesterol) e APOE (apolipoproteína E) influenciam no peso e na resposta do perfil lipídico ao tratamento com G. cambogia. Métodos - Trinta e três pacientes com sobrepeso ou obesidade receberam diariamente uma dose de 2,4g de extrato padronizado de G. cambogia (52,4% de ácido-hidroxicítrico). Antes do início do tratamento e após oito semanas, dados antropométricos e perfil lipídico foram obtidos. Resultados - Após o período de tratamento, não foi possível perceber diferenças na resposta sobre o perfil lipídico entre portadores e não portadores do alelo APOE*2, ou do alelo APOE*4. Uma diferença modesta, porém não significante, foi encontrada na comparação entre portadores e não portadores do alelo B2 (gene CETP) para os níveis de colesterol HDL (p=0,086) e triglicerídeos (p= 0,098). Em relação ao peso, não foram detectadas diferenças na resposta ao tratamento entre os genótipos. Conclusão - Os resultados sugerem que a variante no gene CETP pode estar envolvida na modulação dos níveis de HDL-c após o tratamento com G. cambogia. Entretanto, uma investigação em uma amostra maior será necessária para confirmar esses resultados.
Objective - To investigate the influence of polymorphisms of the CETP (cholesterol ester transfer protein) and APOE (apolipoprotein E) genes on weight changes and lipid levels during the treatment with G. cambogia. Methods - Thirty three patients with overweight or obesity received a daily dose of 2.4 grams of a standardized extract of G. cambogia (52.4% hydroxycitric acid). Before the start of treatment and after eight weeks, lipid profile and anthropometric data were obtained. Results - After the treatment, there were no significant differences in the response of serum lipids between carriers and noncarriers of the allele APOE*2 and APOE*4. A slight difference, but not significant, was observed in the comparison between carriers and noncarriers of allele B2 (CETP gene) for HDL cholesterol levels (p=0,086) and triglycerides levels (p= 0,098). There were no significant differences in the weight after treatment according to genotypes. Conclusion - The results suggest that the variant in the CETP gene may be associated with levels of HDL-c after treatment with G. cambogia. However, an investigation in a larger sample is needed to confirm these results.
Asunto(s)
Humanos , Proteínas de Transferencia de Ésteres de Colesterol , Garcinia cambogia , Farmacogenética , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: A previous study by our research group evaluated the levels of DNA damage using the comet assay in hemodialysis patients with type 2 diabetes mellitus. The same blood samples were also evaluated using the cytochalasin B micronucleus assay. A comparison of the results of the two assays is presented here. METHODS: Whole blood samples were collected from 22 type 2 diabetes mellitus patients on hemodialysis and from 22 control subjects. Samples were collected from patients early in the morning on Mondays, before the first weekly hemodialysis session. The cytokinesis-block micronucleus assay (CBMN) was used to evaluate genomic instability. RESULTS: The frequencies of micronuclei and nuclear buds were higher in patients than in controls (p-value = 0.001 and p-value < 0.001, respectively). There was a correlation between the frequency of micronuclei and DNA damage with the results of the comet assay (p-value < 0.001). The difference in the frequency of micronuclei and nuclear buds between patients and controls was more pronounced in the group with higher median comet values than in the group with lower comet values. CONCLUSIONS: Our results suggest that the increased rates of DNA damage as measured by the comet assay and influenced by the weekly routine therapy of these patients has a mutagenic effect, thereby increasing the risk of cancer in this group.
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Humanos , Ensayo Cometa , Inestabilidad Genómica , Pruebas de Micronúcleos , Diálisis RenalRESUMEN
OBJETIVO: Investigar a influência genética da variante T102C do gene do receptor 2A de serotonina (HTR2A) e sua interação com aspectos do meio ambiente, como exposição a ruídos, trânsito, clima, oportunidades de adquirir novas informações, segurança física e proteção, dentre outras, como possíveis fatores de risco para o desenvolvimento da síndrome da fibromialgia (SFM). MÉTODOS: Foram avaliados 41 pacientes com SFM e 49 indivíduos-controle. Os fatores ambientais foram avaliados pela aplicação do domínio V do questionário WHOQOL-100 (OMS). Solicitou-se aos pacientes que as respostas representassem os momentos antes do surgimento dos sintomas. A variante T102C do gene do receptor 2A de serotonina (HTR2A) foi determinada por PCR-RFLP. RESULTADOS: Na amostra de pacientes, o número de portadores do alelo 102C foi maior do que o encontrado na amostra controle (76,5% vs. 50%; P = 0,028). Os escores do domínio V foram menores em pacientes quando comparados aos controles (P < 0,001). O fator "falta de oportunidades de adquirir novas informações e habilidades" elevou em quase 14 vezes a chance de desenvolvimento da síndrome (P = 0,009). "Baixa qualidade de cuidados sociais e de saúde", somada à presença do alelo 102C, elevou em mais de 90 vezes (P = 0,005). Contudo, indivíduos portadores desse mesmo alelo que possuem alta qualidade de cuidados sociais e de saúde não se encontram sob risco de desenvolver a SFM. CONCLUSÕES: Esses dados sugerem que tais fatores podem predispor à SFM, especialmente em portadores do alelo 102C. Entretanto, são necessárias investigações com amostras maiores.
OBJECTIVES: This study aimed to investigate the genetic influence of the T102C polymorphism of the 2A serotonin receptor gene (HTR2A) and its interaction with environmental aspects, such as exposure to noise, traffic, climate, and opportunities to acquire new information, physical protection, and security, among others, as possible risk factors for developing fibromyalgia syndrome (FMS). METHODS: Forty-one FMS patients and 49 controls were evaluated. Environmental factors were evaluated by application of the V domain of the WHOQOL-100 questionnaire. Patients were asked that their answers represented only the periods preceding the onset of symptoms. The T102C variant of the HTR2A gene was determined through PCR/RFLP. RESULTS: Among patients, the frequency of carriers of the 102C allele was higher than in controls (76.5% vs. 50%; P = 0.028). The scores of the V domain were lower in patients than in controls, indicating a worst perception of the environmental quality by patients (P < 0.001). The factor "lack of opportunities for acquiring new information and skills" increased the chance of developing FMS by almost 14-fold (P = 0.009). The factor "low quality of social care and health" together with the presence of the 102C allele also increased this chance by more than 90-fold (P = 0.005). However, carriers of the same allele who have high quality social care and health are not at a higher risk to develop FMS. CONCLUSION: These data suggest that these factors may predispose to FMS, especially in carriers of the 102C allele. However, studies with larger samples are required to confirm this hypothesis.
Asunto(s)
Femenino , Humanos , Persona de Mediana Edad , Fibromialgia/genética , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Calidad de Vida , /genética , Fibromialgia/etiología , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
OBJECTIVES: This study aimed to investigate the genetic influence of the T102C polymorphism of the 2A serotonin receptor gene (HTR2A) and its interaction with environmental aspects, such as exposure to noise, traffic, climate, and opportunities to acquire new information, physical protection, and security, among others, as possible risk factors for developing fibromyalgia syndrome (FMS). METHODS: Forty-one FMS patients and 49 controls were evaluated. Environmental factors were evaluated by application of the V domain of the WHOQOL-100 questionnaire. Patients were asked that their answers represented only the periods preceding the onset of symptoms. The T102C variant of the HTR2A gene was determined through PCR/RFLP. RESULTS: Among patients, the frequency of carriers of the 102C allele was higher than in controls (76.5% vs. 50%; P = 0.028). The scores of the V domain were lower in patients than in controls, indicating a worst perception of the environmental quality by patients (P < 0.001). The factor "lack of opportunities for acquiring new information and skills" increased the chance of developing FMS by almost 14-fold (P = 0.009). The factor "low quality of social care and health" together with the presence of the 102C allele also increased this chance by more than 90-fold (P = 0.005). However, carriers of the same allele who have high quality social care and health are not at a higher risk to develop FMS. CONCLUSION: These data suggest that these factors may predispose to FMS, especially in carriers of the 102C allele. However, studies with larger samples are required to confirm this hypothesis.
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Fibromialgia/genética , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Calidad de Vida , Receptor de Serotonina 5-HT2A/genética , Femenino , Fibromialgia/etiología , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
Alzheimer's disease is a complex neurodegenerative disorder. Several genes have been suggested as Alzheimer's susceptibility factors, the apolipoprotein E (APOE) gene being an established susceptibility gene and the genes coding angiotensin-converting enzyme (ACE) and apolipoprotein C1 (APOC1) being considered possible candidate genes for the disease. The objective of this study was to investigate the association of ACE and APOC1 gene polymorphisms with susceptibility to Alzheimer's disease and dementia in general, both alone and combined with the APOE gene. Forty-seven patients with dementia in general (35 of them with Alzheimer's disease) and 85 controls were investigated. The haplotypes E*3/-317*ins and E*4/-317*ins of APOE/APOC1 genes were significantly more frequent in the groups with Alzheimer's disease and dementia in general (P < 0.001). The frequency of the ACE*ins allele was also greater in the groups with Alzheimer's disease and dementia in general (P = 0.022; P = 0.045), but genotype frequencies were only different in groups without the E*4/-317*ins haplotype (P = 0.012 for Alzheimer's disease; P = 0.04 for dementia). Our data point to important genetic interactions involved in these diseases.
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Enfermedad de Alzheimer/genética , Apolipoproteína C-I/genética , Apolipoproteínas E/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Anciano , Anciano de 80 o más Años , Brasil , Demencia/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
INTRODUÇÃO: A fibromialgia se trata de uma desordem multifatorial, cuja etiologia reside na interação entre a susceptibilidade genética e o ambiente. No entanto, poucos trabalhos procuram detectar quais seriam os fatores considerados de risco. OBJETIVO: Investigar a influência genética e sua interação com qualidade ambiental e com estresse como possíveis fatores de risco para o desenvolvimento da fibromialgia. PACIENTES E MÉTODOS: Neste estudo transversal, foram investigados dois grupos de mulheres, sendo 47 com diagnóstico clínico de fibromialgia, e 41 mulheres do grupo controle, todas da comunidade de Novo Hamburgo, RS. O polimorfismo do gene da apolipoproteína E (APOE) foi analisado, a partir do DNA extraído do sangue total de ambas as amostras. Os fatores ambientais foram avaliados através do inventário de sintomas para adultos de Lipp (ISSL), para a averiguação do estresse comportamental, e da aplicação do domínio V do WHOQOL-100. RESULTADOS: Dentre as pacientes, foram encontradas mais mulheres com níveis altos de estresse, quando comparado à amostra controle (P < 0,001); além disto, os escores médios do domínio V do WHOQOL-100, que avalia qualidade do meio ambiente, foram inferiores neste grupo (P < 0,001). As frequências genotípicas e alélicas do gene APOE foram similares entre os dois grupos. A análise multivariada demonstrou que baixos escores do WHOQOL-100, aumentaram a chance de desenvolvimento da doença em 57,7 vezes (P < 0,001), e que altos níveis de estresse foram significativamente relacionados com a doença (OR = 197,2; P < 0,001). Essa abordagem apontou para uma interação entre estresse e a presença do alelo E*2 (P = 0,028). A doença foi muito mais frequente em pacientes com altos níveis de estresse que não eram portadoras do alelo E*2 (OR estimado = 265,1), quando comparada a pacientes com o mesmo nível de estresse e portadoras do alelo E*2 (OR estimado = 1,06). CONCLUSÃO: A presença do alelo E*2 pode indicar possível ...
INTRODUCTION: Fibromyalgia is a multifactorial disease, of which etiology is based on interaction between genetic susceptibility and environment. However, few studies attempted to identify the risk factors. OBJECTIVE: To investigate the genetic influence and its interaction with environmental quality and stress, as possible risk factors for fibromyalgia development. PATIENTS AND METHODS: This cross-sectional study investigated two groups of women, of which 47 had a clinical diagnosis of fibromyalgia, and 41 women comprising thre control group, all from the town of Novo Hamburgo, RS. The apolipoprotein E (APOE) gene polymorphism was analyzed in DNA extracted from total blood, in both samples. Environmental factors were studied through Lipp's Inventory of Stress Symptoms for Adults and by applying the WHOQOL-100 domain V. RESULTS: Among the patients, more women had high stress levels when compared to the control sample (P < 0.001); moreover, the average scores of the WHOQOL-100 domain V, which analyze environment quality, were lower in this group (P < 0.001). APOE genotypic and allelic frequencies were similar between the two groups. Multivariate analysis showed that low WHOQOL-100 scores increase the chance of disease development by 57.7 times (P < 0.001), and that high stress levels were related with the disease (OR = 197.2; P < 0.001). This approach pointed out an interaction between stress and presence of E*2 allele (P = 0.028). Fibromyalgia was much more frequent in patients with high stress levels that were E*2 non-carriers (estimated OR = 265.1), when compared to patients with the same stress level, but E*2 carriers (estimated OR = 1.06). CONCLUSION: E*2 allele presence could have a protective action regarding the association between fibromyalgia and stress.
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Femenino , Humanos , Persona de Mediana Edad , Apolipoproteínas E/genética , Ambiente , Fibromialgia/etiología , Predisposición Genética a la Enfermedad , Estrés Psicológico/complicaciones , Estudios Transversales , Fibromialgia/genética , Estudios RetrospectivosRESUMEN
FUNDAMENTO: Baixos níveis de HDL-c são importantes preditores de doença coronariana, a primeira causa de morte no mundo todo. Muitos fatores afetam os níveis de HDL-c, tais como os polimorfismos de genes que codificam proteínas-chave para a via de transporte reverso de colesterol. OBJETIVO: Investigar a influência de sete polimorfismos dos genes CETP, APOA1, ABCA1 e SCARB1 genes nos níveis de HDL-c em uma população da região sul do Brasil. MÉTODOS: Os polimorfismos foram investigados em uma amostra de 500 indivíduos de descendência europeia, mas os níveis de HDL-c de somente 360 indivíduos foram ajustados para cofatores usando regressão linear múltipla no estudo de associação. A amostra foi dividida em tercis de acordo com os níveis ajustados de HDL-c e frequências de alelos e haplótipos foram comparadas entre o 1º e o 3º tercis dos níveis ajustados de HDL-c. RESULTADOS: Quando as combinações dos alelos de risco foram testadas, a frequência de combinações alélicas em três genes (haplótipo 1 do gene APOA1, variante 2S do gene SCARB1, e alelo B1 do gene CETP) foi significantemente mais alta no tercil inferior dos níveis ajustados de HDL-c (28,3 por cento) do que no tercil superior (14,9 por cento; p=0,008), o que indica que a presença dessas variantes aumentou 2,26 vezes a chance de ter níveis de HDL-C < 39,8 mg/dl. CONCLUSÃO: Espera-se que esses marcadores, quando estudados separadamente, tenham uma pequena influência na característica que está sendo analisada, mas uma influência maior foi detectada quando os marcadores foram estudados em combinação. Em uma população da região sul do Brasil, nossos dados mostraram uma influência significante das combinações das variantes dos genes APOA1, SCARB1 e CETP nos níveis de HDL-c.
BACKGROUND: Low HDL-C levels are important predictors of coronary disease, the first cause of death worldwide. Many factors affect HDL-C levels, such as polymorphisms of genes encoding for key proteins of the reverse cholesterol transport pathway. OBJECTIVE: To investigate the influence of seven polymorphisms of the CETP, APOA1, ABCA1 and SCARB1 genes on HDL-C levels in a southern Brazilian population. METHODS: The polymorphisms were investigated in a sample of 500 individuals of European descent, but HDL-C levels from only 360 individuals were adjusted for cofactors using multiple linear regressions in the association study. The sample was divided in tertiles according to adjusted HDL-C levels, and allele and haplotype frequencies were compared between the 1st and 3rd tertiles of adjusted HDL-C levels. RESULTS: When combinations of risk alleles were tested, the frequency of allele combinations in three genes (haplotype 1 of APOA1 gene, variant 2S of SCARB1 gene, and allele B1 of CETP gene) was significantly higher in the lower tertile of adjusted HDL-C (28.3 percent) than in the upper tertile (14.9 percent; p=0.008), which indicated that the presence of these variants increased 2.26 times the chances of having HDL-C levels below 39.8 mg/dl. CONCLUSION: These markers, when studied separately, are expected to have a small influence on the characteristic under analysis, but greater influence was detected when the markers were studied in combination. In a population of southern Brazilians, our data showed a significant influence of variant combinations of APOA1, SCARB1 and CETP genes on HDL-c levels.
FUNDAMENTO: Bajos niveles de HDL-c son importantes predictores de enfermedad coronaria, la primera causa de muerte en todo el mundo. Muchos factores afectan los niveles de HDL-c, tales como los polimorfismos de genes que codifican proteínas-clave para la vía de transporte reverso de colesterol. OBJETIVO: Investigar la influencia de siete polimorfismos de los genes CETP, APOA1, ABCA1 y SCARB1 genes en los niveles de HDL-c en una población de la región sur del Brasil. MÉTODOS: Los polimorfismos fueron investigados en una muestra de 500 individuos de descendencia europea, pero los niveles de HDL-c de solamente 360 individuos fueron ajustados para cofactores usando regresión lineal múltiple en el estudio de asociación. La muestra fue dividida en terciles de acuerdo con los niveles ajustados de HDL-c y frecuencias de alelos y haplotipos fueron comparadas entre el 1º y el 3º terciles de los niveles ajustados de HDL-c. RESULTADOS: Cuando las combinaciones de los alelos de riesgo fueron probadas, la frecuencia de combinaciones alélicas en tres genes (haplotipo 1 del gen APOA1, variante 2S del gen SCARB1, y alelo B1 del gen CETP) fue significativamente más alta en el tercil inferior de los niveles ajustados de HDL-c (28,3 por ciento) que en el tercil superior (14,9 por ciento; p=0,008), lo que indica que la presencia de esas variantes aumentó 2,26 veces la posibilidad de tener niveles de HDL-C < 39,8 mg/dl. CONCLUSIÓN: Se espera que esos marcadores, cuando sean estudiados separadamente, tengan una pequeña influencia en la característica que está siendo analizada, pero una influencia mayor fue detectada cuando los marcadores fueron estudiados en combinación. En una población de la región sur del Brasil, nuestros datos mostraron una influencia significativa de las combinaciones de las variantes de los genes APOA1, SCARB1 y CETP en los niveles de HDL-c.