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Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.
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Neoplasias da Vesícula Biliar , Cálculos Biliares , Idoso , Humanos , Estudos de Casos e Controles , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/genética , Cálculos Biliares/epidemiologia , Cálculos Biliares/genética , Cálculos Biliares/complicações , Incidência , Estudos Retrospectivos , Fatores de Risco , Masculino , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract. Most cases of GBC are diagnosed in low-income and middle-income countries, and research into this disease has long been limited. In this study we therefore investigate the epigenetic changes along the model of GBC carcinogenesis represented by the sequence gallstone disease â dysplasia â GBC in Chile, the country with the highest incidence of GBC worldwide. APPROACH AND RESULTS: To perform epigenome-wide methylation profiling, genomic DNA extracted from sections of formalin-fixed, paraffin-embedded gallbladder tissue was analyzed using Illumina Infinium MethylationEPIC BeadChips. Preprocessed, quality-controlled data from 82 samples (gallstones n = 32, low-grade dysplasia n = 13, high-grade dysplasia n = 9, GBC n = 28) were available to identify differentially methylated markers, regions, and pathways as well as changes in copy number variations (CNVs). The number and magnitude of epigenetic changes increased with disease development and predominantly involved the hypermethylation of cytosine-guanine dinucleotide islands and gene promoter regions. The methylation of genes implicated in Wnt signaling, Hedgehog signaling, and tumor suppression increased with tumor grade. CNVs also increased with GBC development and affected cyclin-dependent kinase inhibitor 2A, MDM2 proto-oncogene, tumor protein P53, and cyclin D1 genes. Gains in the targetable Erb-B2 receptor tyrosine kinase 2 gene were detected in 14% of GBC samples. CONCLUSIONS: Our results indicate that GBC carcinogenesis comprises three main methylation stages: early (gallstone disease and low-grade dysplasia), intermediate (high-grade dysplasia), and late (GBC). The identified gradual changes in methylation and CNVs may help to enhance our understanding of the mechanisms underlying this aggressive disease and eventually lead to improved treatment and early diagnosis of GBC.
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Metilação de DNA , Epigênese Genética , Neoplasias da Vesícula Biliar/genética , Cálculos Biliares/genética , Hiperplasia/genética , Carcinogênese , Linhagem Celular Tumoral , Variações do Número de Cópias de DNA , Feminino , Genes Neoplásicos/genética , Humanos , MasculinoRESUMO
BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10-5 ) and Europeans (P = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.
Assuntos
Índice de Massa Corporal , Proteína C-Reativa/análise , Neoplasias da Vesícula Biliar/etiologia , Cálculos Biliares/complicações , Adulto , Fatores Etários , Chile/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/genética , Cálculos Biliares/epidemiologia , Predisposição Genética para Doença/genética , Variação Genética , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Gallbladder cancer (GBC), although infrequent in industrialized countries, has high incidence rates in certain world regions, being a leading cause of death among elderly Chilean women. Surgery is the only effective treatment, and a five-year survival rate of advanced-stage patients is less than 10%. Hence, exploring immunotherapy is relevant, although GBC immunogenicity is poorly understood. This study examined the relationship between the host immune response and GBC patient survival based on the presence of tumor-infiltrating lymphocytes at different disease stages. METHODS: Tumor tissues from 80 GBC patients were analyzed by immunohistochemistry for the presence of CD3+, CD4+, CD8+, and Foxp3+ T cell populations, and the results were associated with clinical stage and patient survival. RESULTS: The majority of tumor samples showed CD3+ T cell infiltration, which correlated with better prognosis, particularly in advanced disease stages. CD8+, but not CD4+, T cell infiltration correlated with improved survival, particularly in advanced disease stages. Interestingly, a < 1 CD4+/CD8+ T cell ratio was related with increased survival. Additionally, the presence of Foxp3+ T cells correlated with decreased patient survival, whereas a ≤ 1 Foxp3+/CD8+ T cell ratio was associated with improved patient survival. CONCLUSIONS: Depending on the disease stage, the presence of CD8+ and absence of Foxp3+ T cell populations in tumor tissues correlated with improved GBC patient survival, and thus represent potential markers for prognosis and management of advanced disease, and supports testing of immunotherapy.
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Linfócitos T CD8-Positivos/imunologia , Quimiorradioterapia Adjuvante/mortalidade , Fatores de Transcrição Forkhead/metabolismo , Neoplasias da Vesícula Biliar/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Adulto , Idoso , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/imunologia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVE: The purpose of this study was to describe the feasibility of respiratory oscillometry (RO) in schoolchildren with asthma, and the concordance of its results with those of spirometry, to determine its clinical usefulness. METHODS: RO and spirometry were performed in 154 children (6 to 14-year-old) with asthma, following strict quality criteria for the tests. Their feasibility (probability of valid test, time of execution, number of maneuvers needed to achieve a valid test, and perceived difficulty) was compared. The factors that influence feasibility were analyzed with multivariate methods. FEV1, FEV1/FVC, FVC and FEF25-75 for spirometry, and R5, AX and R5-19 for RO, were converted into z-scores and their concordance was investigated through intraclass correlation coefficients (ICC) and kappa indices for normal/abnormal values. RESULTS: There were no differences in the probability of obtaining a valid RO or spirometry (83.1% vs. 81.8%, p = 0.868). RO required a lower number of maneuvers [mean (SD) 4.2 (1.8) versus 6.0 (1.6), p < 0.001] and less execution time [5.1 (2.7) versus 7.6 (2.4) minutes, p < 0.001], and patients considered it less difficult. Age increased the probability of obtaining valid RO and spirometry. The concordance of results between RO and spirometry was low, and only between zFEV1 and zAX could it be considered moderate (ICC = 0.412, kappa = 0.427). CONCLUSION: RO and spirometry are feasible in children with asthma. RO has some practical advantages, but the concordance of its results with spirometry is low.
Assuntos
Asma , Criança , Humanos , Adolescente , Oscilometria/métodos , Estudos de Viabilidade , Asma/diagnóstico , Espirometria/métodos , Volume Expiratório ForçadoRESUMO
A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.
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For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function. Starting from the main questions "Is Se deficiency related to heart inflammation and arrhythmogenesis in CCC?" and "Could Se be recommended as a therapeutic strategy for CCC?", we show evidence implicating the complex and multidetermined CCC physiopathology, discussing its possible interplays with the multifunctional cytokine TGF-ß as regulators of immune response and fibrosis. We present two new proposals to face this global public health challenge in vulnerable populations affected by this parasitic disease: fibrosis modulation mediated by TGF-ß pathways and the possible use of selenoproteins as antioxidants regulating the increased reactive oxygen stress present in CCC inflammatory environments. We assess the opportunity to consider the beneficial effects of Se in preventing heart failure as a concept to be applied for CCC patients.
Assuntos
Doença de Chagas , Doenças Transmissíveis , Insuficiência Cardíaca , Selênio , Trypanosoma cruzi , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Fibrose , Humanos , Selênio/uso terapêutico , Fator de Crescimento Transformador beta , Trypanosoma cruzi/fisiologiaRESUMO
Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence "gallstones â dysplasia â GBC". In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04-1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.
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Familial aggregation of endemic congenital hypothyroidism (CH) in an iodine-deficient population from northern Congo (Democratic Republic (DR)) was analysed on data collected four decades ago (1979-1980). During a systematic survey of 62 families, 46 endemic CH subjects (44 myxedematous and 2 neurological) were identified based on clinical evidence within a village cohort of 468 subjects. A distribution analysis showed that two families presented significant excess of cases versus a random background distribution. Both families were characterised by two healthy parents having all of their five offspring affected by some form of endemic CH. Goitre prevalence in endemic CH was lower than that in the general population, while goitre prevalence in the unaffected part of the cohort (parents and siblings) was similar to that of the general population. Some unidentified genetic/epigenetic factor(s) could contribute to the evolution of some iodine-deficient hypothyroid neonates through irreversible and progressive loss of thyroid functional capacity during early childhood (<5 years old). Besides severe iodine deficiency, environmental exposure to thiocyanate overload and selenium deficiency, factors not randomly distributed within families and population, intervened in the full expression of endemic CH. Further exploration in the field will remain open, as iodine deficiency in Congo (DR) was eliminated in the 1990s.
Assuntos
Hipotireoidismo Congênito/epidemiologia , Bócio Endêmico/epidemiologia , Iodo/deficiência , Selênio/deficiência , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Hipotireoidismo Congênito/genética , República Democrática do Congo/epidemiologia , Exposição Ambiental/efeitos adversos , Feminino , Bócio Endêmico/genética , Humanos , Lactente , Recém-Nascido , Masculino , Linhagem , Fenótipo , Prevalência , Tiocianatos/toxicidade , Adulto JovemRESUMO
BACKGROUND: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. METHODS: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. RESULTS: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. CONCLUSION: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Neoplasias da Vesícula Biliar/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Chile/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Estudos de Associação Genética , Humanos , Indígenas Sul-Americanos/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , População Branca/genéticaRESUMO
INTRODUCTION: The health-related quality of life (HRQoL) questionnaire is important in order to assess the effects of therapeutic intervention. The aim of this study is to analyse HRQoL, comparing cases of attention deficit hyperactivity disorder (ADHD) treated with methylphenidate (ADHD-T), untreated cases (ADHD-N), and controls. MATERIAL AND METHODS: The study included a sample of 228 participants between 8 and 14 years old (114 controls, 57 ADHD-T, and 57 ADHD-N). Consecutive sampling was used in ADHD according to DSM-IV criteria (ADHD Rating Scales IV), and random sampling of controls matched by gender and age. The evaluation of HRQoL was made by using KIDSCREEN-52 parent version. RESULTS: The intensity of ADHD symptoms is significantly lower in ADHD-T than in ADHD-N. There is a moderate significant correlation between greater intensity of ADHD symptoms and worse HRQoL. ADHD cases have significantly worse HRQoL than controls on psychic well-being, mood, relationship with parents and friends, school environment, and social acceptance. The cases of ADHD-T have significantly better HRQoL than ADHD-N in the school dimension, but do not differ significantly in other dimensions of KIDSCREEN-52. CONCLUSIONS: It would be advisable that the treatment of ADHD integrates multi-dimensional therapeutic models that improve the basic symptoms of the disorder, as well as the HRQoL.
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Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Qualidade de Vida , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Paraneoplastic syndromes can be presented in multiple ways, which include endocrinological, hematologic, rheumatologic and nephrologic manifestations. While most of the publications described solid tumors as responsible for these manifestations, hematologic neoplasms are important cause to consider as part of the differential diagnosis. We report the case of a 46 year-old man with seronegative symmetric polyarthritis of large and small joints associated with membranoproliferative glomerulonephritis with deposits of immune complexes and acute impairment of renal function, as part of a paraneoplastic syndrome secondary of a classical Hodgkin lymphoma with bone marrow invasion, which reversed completely with chemotherapy treatment.
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Artrite/etiologia , Glomerulonefrite Membranoproliferativa/etiologia , Doença de Hodgkin/diagnóstico , Síndromes Paraneoplásicas/etiologia , Artrite/diagnóstico , Diagnóstico Diferencial , Glomerulonefrite Membranoproliferativa/diagnóstico , Doença de Hodgkin/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/diagnósticoRESUMO
Pathogens may impair reproduction in association or not with congenital infections. We have investigated the effect of acute infection with Trypanosoma cruzi, the protozoan agent of Chagas disease, on reproduction of female mice. In the acute, parasitemic, phase of the infection, female mice were totally unable to reproduce. Most of them (80%) were infertiles and did not develop any gestation. In the few gravid infected mice, implantation numbers were as in uninfected control mice. However, their fetuses presented a weight meanly reduced by 40% as compared to those of uninfected females, and all of them died during the gestation or whithin 48 h after birth. Such massive mortality did not result from congenital infection, which did not occur. The infertility and the fetal mortality occuring early in gestation (resorptions) were significantly correlated with a high maternal parasitemia, whereas later fetal mortality was associated with the presence of intracellular parasites in the utero-placental unit. The decidua was particularly receptive to T. cruzi multiplication, since this tissue harboured 125 fold more amastigotes than the maternal heart or other placental tissues. In addition, placentas of dead fetuses presented histopathological lesions (inflammatory infiltrates, fibrine deposits and ischemic necrosis). Such harmfull effects of acute infection were not observed when female mice were in the chronic phase of the infection, since these reproduce normally. Their fetuses only suffered from moderate and reversible growth retardation. These results indicate that, following the maternal parasite burden, T. cruzi infection may induce very deleterious effects on gestation.
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Doença de Chagas/complicações , Morte Fetal/parasitologia , Infertilidade/parasitologia , Complicações Parasitárias na Gravidez , Trypanosoma cruzi , Doença Aguda , Animais , Doença Crônica , Feminino , Morte Fetal/patologia , Camundongos , Camundongos Endogâmicos BALB C , Necrose , Placenta/parasitologia , Gravidez , Trypanosoma cruzi/patogenicidadeRESUMO
Selenium (Se) deficiency is linked with some cardiomyopathies. Its status was determined in 170 patients with chronic Chagas' disease from 2 Brazilian regions (Rio de Janeiro and Belo Horizonte), clinically stratified into groups as follows: indeterminate or asymptomatic (IND); cardiac asymptomatic (CARDa); cardiac symptomatic with moderate to severe heart dysfunction (CARDb); and healthy adults (HA), used for comparison. In most HA, Se levels were normal, excluding an overall Se deficiency. Se was significantly lower in CARDb than in HA, IND, or CARDa patients. This was not associated with a concomitant decrease in activity of glutathione peroxidase. Thyrotropin was normal, excluding iodine deficiency. Se correlated positive and significantly with ventricular ejection fraction (assessed via echocardiography). Asymptomatic children with acute Chagas' disease had normal Se as well as 5 noninfectious cases of cardiomyopathy. Low Se was found in 6 of 10 chagasic patients with digestive megasyndromes. Thus, the decrease in Se in chagasic patients seems to be a biological marker for Trypanosoma cruzi infection and related to the progression of pathology.
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Cardiomiopatia Chagásica/fisiopatologia , Glutationa Peroxidase/sangue , Selênio/deficiência , Animais , Anticorpos Antiprotozoários/sangue , Brasil , Cardiomiopatia Chagásica/imunologia , Doença de Chagas/imunologia , Doença de Chagas/fisiopatologia , Criança , Progressão da Doença , Humanos , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Análise de Regressão , Selênio/sangue , Tireotropina/sangue , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/isolamento & purificaçãoRESUMO
INTRODUCTION: Oppositional defiant disorder (ODD) is characterized by a pattern of negative, defiant, disobedient and hostile behavior toward authority figures. ODD is one of the most frequent reasons for clinical consultation on mental health during childhood and adolescence. ODD has a high morbidity and dysfunction, and has important implications for the future if not treated early. OBJECTIVE: To determine the prevalence of ODD in schoolchildren aged 6-16 years in Castile and Leon (Spain). MATERIAL AND METHODS: Population study with a stratified multistage sample, and a proportional cluster design. Sample analyzed: 1,049. Cases were defined according to DSM-IV criteria. RESULTS: An overall prevalence rate of 5.6% was found (95% CI: 4.2%-7%). Male gender prevalence=6.8%; female=4.3%. Prevalence in secondary education=6.2%; primary education=5.3%. No significant differences by gender, age, grade, type of school, or demographic area were found. ODD prevalence without considering functional impairment, such as is performed in some research, would increase the prevalence to 7.4%. ODD cases have significantly worse academic outcomes (overall academic performance, reading, maths and writing), and worse classroom behavior (relationship with peers, respect for rules, organizational skills, academic tasks, and disruption of the class). CONCLUSIONS: Castile and Leon has a prevalence rate of ODD slightly higher to that observed in international publications. Depending on the distribution by age, morbidity and clinical dysfunctional impact, an early diagnosis and a preventive intervention are required for health planning.
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Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Adolescente , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico , Criança , Feminino , Humanos , Masculino , Prevalência , Espanha/epidemiologiaRESUMO
Micronutrient deficiencies and infectious disease often coexist and show complex interactions leading to mutually reinforced detrimental clinical effects. Such a combination is predominantly observed in underprivileged people of developing countries, particularly in rural regions. Several micronutrients such as trace elements (zinc, iron, selenium) modulate immune function and influence the susceptibility of the host to infection. Nevertheless, the effect of individual micronutrients on components of innate immunity is difficult to design and interpret. Micronutrient deficiency, in general, has a widespread effect on nearly all components of the innate immune response. Chagas' disease is a pertinent model to study interaction of nutrition, immunity and infection, as it implies many components of innate immunity. An important question is whether alterations on micronutrient intake modify the course of infection. Some interactions of trace elements with innate immunity and acute inflammatory response are reviewed in this article with a special focus on selenium deficiency and Trypanosoma cruzi infection.
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Imunidade Inata/fisiologia , Parasitos/imunologia , Oligoelementos/fisiologia , Reação de Fase Aguda/imunologia , Animais , Humanos , Deficiências de Ferro , Modelos Biológicos , Nematoides/imunologia , Selênio/deficiência , Trypanosoma cruzi/imunologia , Zinco/deficiênciaRESUMO
Chagasic patients with cardiomyopathy have low levels of selenium (Se), a fundamental trace element. We evaluated the effect of supplementing infected mice with Se (0.25-16 ppm). Supplementation with 0.25 or 1 ppm Se led to parasitaemia and survival curves similar to those of the control group. Mice treated with 4-16 ppm showed a dose-dependent decrease of parasitaemia, significant for the highest concentration. This was probably due to a direct effect on the parasites, which were lysed after in vitro incubation with Se. Survival rates did not change significantly; however, heart damage was reduced in infected mice supplemented with 4 ppm Se, as indicated by a lower cardiac isoform of creatine kinase levels. Our results imply that Se supplementation does not lead to a general protection during infection, but may help protect the heart from inflammatory damage. The effect of Se supplementation in the course of T. cruzi infection depends on the host-parasite pair employed.
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Cardiomiopatia Chagásica/tratamento farmacológico , Suplementos Nutricionais , Miocárdio/patologia , Selênio/uso terapêutico , Doença Aguda , Animais , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/patologia , Doença Crônica , Relação Dose-Resposta a Droga , Feminino , Camundongos , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Parasitemia/patologia , Selênio/administração & dosagem , Resultado do Tratamento , Trypanosoma cruzi/patogenicidadeRESUMO
Selenium is an essential trace element and its deficiency was implicated in heart diseases. We recently showed low Se levels in chronic chagasic patients with cardiomyopathy. Herein, mice were depleted in Se by feeding the mothers with chow containing only 0.005 mg Se/kg and maintaining this diet for offspring, that were further infected with Trypanosoma cruzi. Survival rate was significantly lower in Se deficient than in control mice. Parasitemia was similar in all groups. Necrotic heart lesions were found after infection (high CK-MB levels). No outbreaks of parasite growth were detected in chronic survivors submitted or not to a second Se depletion. The present results confirm our hypothesis that a nutritional deficiency in Se is associated to a higher mortality during T. cruzi infection. The potential beneficial effect of Se supplementation is a perspective. Hypothesis to explain the higher susceptibility of Se-depleted mice to T. cruzi infection are discussed.
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Doença de Chagas/mortalidade , Parasitemia/mortalidade , Selênio/deficiência , Animais , Cardiomiopatia Chagásica/patologia , Doença de Chagas/complicações , Doença de Chagas/imunologia , Doença Crônica , Creatina Quinase/sangue , Creatina Quinase Forma MB , Suscetibilidade a Doenças , Feminino , Isoenzimas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Necrose , Parasitemia/complicações , Parasitemia/imunologia , Gravidez , Taxa de SobrevidaRESUMO
Objetivo: Describir las características clínicas y epidemiológicas de la epilepsia-ausencias en niños en el Hospital Nacional Cayetano Heredia (HNCH). Materiales y Métodos: Estudio descriptivo-retrospectivo. Se identificaron los pacientes con diagnóstico de ausencias del Servicio de Neuropediatría atendidos desde enero de 1998 hasta diciembre del 2002. Criterios de inclusión: manifestaciones clínicas de ausencias y electroencefalograma característico. Exclusión: pacientes con lesiones cerebrales. Resultados: Se incluyeron 33 pacientes (6.4 por ciento del total). La edad promedio al inicio de enfermedad fue 6.6 años, sexo femenino: 54.5 por ciento y tiempo de enfermedad antes del diagnóstico: 12.5 meses. Presentaron antecedente familiar de convulsiones 30.3 por ciento y antecedente de eventos perinatales adversos 18.2 por ciento. El 39.4 por ciento de pacientes presentó ausencias simples y 60.6 por ciento ausencias complejas. El 36.4 por ciento tuvo inicialmente un patrón electroencefalográfico bilateral asimétrico que posteriormente se tornó simétrico. Todos recibieron ácido valproico pero en 6 por ciento se tuvo que cambiar de medicación debido a efectos adversos y 12 por ciento tuvieron que recibir terapia combinada por falta de control. Edad, sexo, tipo de crisis, EEG, antecedentes familiares o perinatales no influyeron en las características clínicas, electroencefalográficas o respuesta terapéutica. Conclusión: Las ausencias complejas con automatismos son las más frecuentes y el ácido valproico es un tratamiento efectivo. El tiempo de enfermedad antes del diagnóstico fue 12.5 meses por lo cual se recomienda mayor difusión a nivel de padres, educadores y personal de salud para diagnósitco y control oportunos.