Childhood Adrenocortical Tumours: a Review

Childhood adrenocortical tumour (ACT) is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6%) or mixed with Cushing's syndrome (42.0%) was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate

Tumor adrenocortical em crianças : avaliação da relação com cancer em familiares e com alterações no gene TP53

Orientador: Romolo SandriniDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós graduação em PediatriaResumo:O tumor de córtex de supra-renal é raro em crianças. Contudo, sua incidência está aumentada na Região Sul do Brasil e no Estado de São Paulo. O tumor adrenocortical é freqüentemente associado ao síndrome de Li-Fraumeni. Foram avaliados 51 pacientes com diagnóstico de tumor de córtex adrenocortical. Obteve-se a história de câncer em familiares de 48 pacientes, provenientes de 46 famílias. Utilizouse o índice relativo de grau de parentesco genético para avaliar a probabilidade de transmissão de um gene comum associado com cânceres familiares. Foi realizado o seqüenciamento do gene TP53 a partir de sangue total em 31 pacientes e 12 familiares. A mediana de idade dos pacientes foi de 2,3 anos; a relação sexo feminino:masculino de 3,3:1. Das 46 famílias estudadas, 8 não apresentaram história familiar de presença de câncer, 24 apresentavam casos esporádicos de câncer (índice relativo de grau de parentesco genético entre 0,12 e 1,1) e 14 famílias com freqüência aumentada de câncer (índice maior que 1,1), porém nenhuma delas preenche os critérios para o diagnóstico de síndrome de Li-Fraumeni ou "Li-Fraumeni-like"'. Em 2 pacientes foram estudados os exons 5 a 9 e em 29 pacientes os exons 2 a 11. O seqüenciamento do gene apresentou mutação no exon 10, codon 337, base 1010, com substituição de arginina (CGC) por histidina (CAC) em todas as amostras cujo exon 10 foi avaliado. As mães de 6 pacientes apresentaram a mesma mutação; sendo que em 2 famílias as mães apresentavam a mutação e os pais eram normais; em outra família, a amostra da mãe era mutada e a dos três irmãos do paciente eram normais; 1 mãe apresentou o seqüenciamento do gene TP53 normal. Treze amostras de pacientes de um centro norte-americano foram utilizados como comparação; destes, 3 apresentaram mutação nos exons 6, codons 196, 213 e 219, e um no exon 7, codon 248; 9 mostraram seqüenciamento normal. Concluiu-se que a presença de tumores adrenocorticais na infância, em nossa região, não está associada à presença de cânceres em familiares, contudo está relacionada à mutação germinativa do p53, no exon 10, codon 337 com substituição de arginina por histidina.Abstract: An adrenocortical tumor occurs rarely in children. The actual incidence of this tumor is unknown but it is estimated to be 0.3 cases per million per year in children under 16 years. The incidence of childhood adrenocortical tumors (ACT) is relatively higher in southern Brazil. This high incidence seems to be restricted to only two Brazilian states: Sao Paulo and Parana. An unexpected high incidence of this tumor is also noted among individuals carrying germline p53 mutations (Li-Fraumeni Familial Cancer Syndrome). Detailed family cancer histories were obtained in 46.families of 48 Brazilian patients with ACT. None of these families had history of cancer similar to that of the Li-Fraumeni Syndrome. The probability of the transmission of a common gene associated with cancer was estimated by the method of genetic relative index. Of 46 families, eight did not have history of cancer (index: zero), 24 had sporadic cases of cancer (index: 0.12-1.1) and 14 families had an apparent increased incidence o f cancer (index: >1.1). Sequence analysis of the p53 gene, exons 2 to 11, was performed in 29 patients. Additional 2 patients had this analysis limited to exons 5 to 9. DNA sequencing in all patients, for whom the exon 10 was analyzed, showed a specific mutation in codon 337, with a substitution of arginine by histidine. No patient had mutations in exons 5 through 9 that are typically mutate in the Li-Fraumeni Syndrome. The mothers o f six patients were also positive for the mutation; one mother had normal p53 sequencing. In three diverse families, in which the mothers were positive for the p53 mutation, two fathers and three siblings of a same family did not have this genetic abnormality. For comparison, of 13 patients admitted to St. Jude Children Research Hospital in Memphis, three had mutations in the p53 gene exons 6 and one in exon 7. Nine patients had normal p53 sequences. Four of these latter patients had extended p53 analysis that included the exon 10 and in all of them, there were no abnormalities. In conclusion, family members of children with ACT from southern Brazil do not present the spectrum o f cancer seen in the LiFraumeni Syndrome. Moreover, they do not exhibit the p53 mutations usually associated with the Li-Fraumeni Syndrome. However, it appears that a specific mutation in the exon 10 of the p53 gene is associated with ACT in these children

Fatores de risco no desenvolvimento da aterosclerose na infância e adolescência Risk factors for the development of atherosclerosis in childhood and adolescence

As doenças cardiovasculares (DCV) constituem uma importante causa de morte nos países desenvolvidos e também naqueles em desenvolvimento. Em geral, as manifestações clínicas das DCV, como infarto do miocárdio, acidente vascular encefálico e doença vascular periférica, são causadas por um processo aterosclerótico e têm início a partir da meia-idade. No entanto, estudos atuais indicam que o processo aterosclerótico começa a se desenvolver na infância. A fisiopatogenia da aterosclerose tem sido estudada pelo seu aspecto inflamatório, e, dentre os marcadores inflamatórios, a proteína-C-reativa (PCR) vem sendo bastante estudada nos indivíduos portadores de alguma DCV, inclusive naqueles aparentemente saudáveis. Níveis elevados de PCR têm sido relacionados a fatores de risco para a aterosclerose: história familiar de doença arterial coronariana (DAC), dislipidemia, hipertensão arterial, diabete melito, obesidade, tabagismo e sedentarismo. Grande parte desses fatores de risco pode ser influenciada por modificações no estilo de vida, tais como a mudança de hábitos alimentares e a prática de atividade física. Na literatura estão documentados os efeitos da atividade física sobre os níveis de PCR na fase adulta, porém há pouco conhecimento dos estilos de vida ativo ou sedentário em crianças e adolescentes. Este trabalho tem o objetivo de revisar o impacto da atividade física em crianças e adolescentes sobre os níveis de PCR e os fatores de risco para o desenvolvimento de DCV.Cardiovascular diseases (CVD) are a major cause of death in developed countries as well as in developing countries. In general, the clinical manifestations of CVD, such as myocardial infarction, stroke and peripheral vascular disease, are caused by an atherosclerotic process with onset as from the middle age. However, current studies indicate that the atherosclerotic process starts to develop in childhood. The pathogenesis of atherosclerosis has been studied as to its inflammatory aspect. Among the inflammatory markers, C-reactive protein (CRP) has been extensively studied in individuals with CVD, including those apparently healthy. High CRP levels have been related to risk factors for atherosclerosis: family history of coronary artery disease (CAD), dyslipidemia, hypertension, diabetes mellitus, obesity, smoking and sedentary lifestyle. A great part of these risk factors may be influenced by lifestyle modifications, such as changes in eating habits and engagement in physical activities. The effects of physical activity on CRP levels in adulthood are documented in the literature, however little is known on the influence of an active or sedentary lifestyle of children and adolescents on CRP levels. Thus, the objective of this study is to review the impact of physical activity of children and adolescents on CRP levels and the risk factors for the development of CVD

Abiotic Stress and Belowground Microbiome: The Potential of Omics Approaches

Nowadays, the worldwide agriculture is experiencing a transition process toward more sustainable production, which requires the reduction of chemical inputs and the preservation of microbiomes’ richness and biodiversity. Plants are no longer considered as standalone entities, and the future of agriculture should be grounded on the study of plant-associated microorganisms and all their potentiality. Moreover, due to the climate change scenario and the resulting rising incidence of abiotic stresses, an innovative and environmentally friendly technique in agroecosystem management is required to support plants in facing hostile environments. Plant-associated microorganisms have shown a great attitude as a promising tool to improve agriculture sustainability and to deal with harsh environments. Several studies were carried out in recent years looking for some beneficial plant-associated microbes and, on the basis of them, it is evident that Actinomycetes and arbuscular mycorrhizal fungi (AMF) have shown a considerable number of positive effects on plants’ fitness and health. Given the potential of these microorganisms and the effects of climate change, this review will be focused on their ability to support the plant during the interaction with abiotic stresses and on multi-omics techniques which can support researchers in unearthing the hidden world of plant–microbiome interactions. These associated microorganisms can increase plants’ endurance of abiotic stresses through several mechanisms, such as growth-promoting traits or priming-mediated stress tolerance. Using a multi-omics approach, it will be possible to deepen these mechanisms and the dynamic of belowground microbiomes, gaining fundamental information to exploit them as staunch allies and innovative weapons against crop abiotic enemies threatening crops in the ongoing global climate change context

Real-time PCR-based quantification of Toxoplasma gondii in tissue samples of serologically positive outdoor chickens

This study aimed to quantify Toxoplasma gondii in tissue samples of serologically positive chickens using real-time polymerase chain reaction (PCR). Of 65 chickens evaluated, 28 were positive for T. gondii antibodies. Brain and heart samples were collected from 26 seropositive chickens and DNA was extracted using Trizol® and amplified using real-time PCR with SYBR® Green. Parasite DNA was detected in 24 of the 26 samples analyzed; the number of positive tissue samples and the parasite quantity did not differ between tissue types. The results confirmed the analytical sensitivity of parasite detection in chicken tissue samples and demonstrated the possibility of using other molecular systems for genotypic analysis

Association between vitamin D deficiency, adiposity and solar exposure in participants with arterial hypertension and diabetes mellitus

Currently, several studies have shown a relationship between vitamin D deficiency and type 2 diabetes mellitus, obesity and hypertension. The major cause of vitamin D deficiency is the lack of adequate sun exposure. The objective of the study was to evaluate serum vitamin D level and to verify its association with vitamin D ingestion, body composition and solar exposure in patients participating in the Hypertension and Diabetes System in Cascavel, PR. A total of 304 adult and elder patients from both genders participated in the study. Demographic and anthropometric data, lifestyle, presence of previous diseases, dietary and serum levels of vitamin D were evaluated. We used the chi square test for association verification and compliance and the Kruskal-Wallis test to compare medians between variables. It was verified serum 25-hydroxyvitamin D (25(OH)D) deficiency (&lt;20ng/mL) in 52.6%, overweight and obesity in 73.4%, increase in abdominal circumference in 77.6% and in body fat percentage in 95.6% of the patients. There was no association between ingestion and serum vitamin D levels. Significant association was found between abdominal circumference (p</p