Heterozigose para mutação no gene CYP21A2 considerada como deficiência de 21-hidroxilase na triagem neonatal

Steroid 21-hydroxylase deficiency (21-OHD) accounts for more than 90% of congenital adrenal hyperplasia. CAH newborn screening, in general, is based on 17-hydroxyprogesterone dosage (17-OHP), however it is complicated by the fact that healthy preterm infants have high levels of 17-OHP resulting in false positive cases. We report on molecular features of a boy born pre-term (GA = 30 weeks; weight = 1,390 g) with elevated levels of 17-OHP (91.2 nmol/L, normal < 40) upon neonatal screening who was treated as having CAH up to the age of 8 months. He was brought to us for molecular diagnosis. Medication was gradually suspended and serum 17-OHP dosages mantained normal. The p.V281L mutation was found in compound heterozygous status with a group of nucleotide alterations located at the 3' end intron 4 and 5' end exon 5 corresponding to the splice site acceptor region. Molecular studies continued in order to exclude the possibility of a nonclassical 21-OHD form. The group of three nucleotide changes was demonstrated to be a normal variant since they failed to interfere with the normal splicing process upon minigene studies.A deficiência de 21-hidroxilase (21-OHD) é uma doença autossômica recessiva que contribui com mais de 90% dos casos de hiperplasia congênita da adrenal. O teste de dosagem de 17-hidroxiprogesterona (17-OHP) por radioimunoensaio em amostras de sangue colhidas em papel de filtro tem sido o método mais usado nos programas de triagem neonatal. No entanto, essa triagem pode apresentar alto número de falso-positivos pelo fato de os recém-nascidos prematuros apresentarem dosagens mais elevadas deste esteróide. Apresentamos aqui os estudos moleculares de uma criança, sexo masculino, nascida pré-termo (IG = 30 sem; peso = 1.390 g) que apresentava valores elevados de 17-OHP sérica (91,2 nmol/L, normal < 40) na triagem neonatal e que foi tratada como portadora da forma clássica da 21-OHD até a idade de 8 meses quando nos foi encaminhada para diagnóstico molecular. A terapia foi, então, gradativamente descontinuada, sendo que as concentrações séricas de 17-OHP se mantiveram normais. A mutação p.V281L foi encontrada em heterozigose composta com um grupo de alterações no terminal 3' do íntron 4 e no terminal 5' do éxon 5 correspondendo à região do sítio aceptor de splicing. A análise do gene CYP21A2 prosseguiu para se excluir a possibilidade de a criança ser afetada com a forma não-clássica de 21-OHD. Pela análise de minigene ficou demonstrado que o grupo de três trocas nucleotídicas não afeta o processo normal de transcrição. Concluindo, a criança é apenas heterozigota da mutação p.V281L sem necessidade de tratamento.13881392Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

A self-organizing map clustering approach to support territorial zoning

This work aims to evaluate three strategies for analyzing clusters of ordinal categorical data (thematic maps) to support the territorial zoning of the Alto Taquari basin, MS/MT. We evaluated a model-based method, another based on the segmentation of the multi-way contingency table, and the last one based on the transformation of ordinal data into intervals and subsequent analysis of clusters from a proposed method of segmentation of the Self-Organizing Map after the neural network training process. The results showed the adequacy of the methods based on the Self-Organizen Map and the segmentation of the contingency table, as these techniques generated unimodal clusters with distinguishable groups.Supported by National Council for Scientific and Technological Development –CNPq, Brazil, and by National Funds through the Portuguese funding agency, FCT -Fundação para a Ciência e a Tecnologia within project 2022.06822.PTDC. The work of Pedro Oliveira was also supported by the doctoral Grant PRT/BD/154311/2022 financed by the Portuguese Foundation for Science and Technology (FCT), and with funds from European Union, under MIT Portugal Progra

Mutagenicactivity of glycoallkaloids from Solanum palinacanthum Dunal (Solanaceae) found in the brazilian cerrado

Solanaceous plants are widely distributed around the world and they are traditionally used as drugs for the treatment of cancer and herpes, and include familiar foods such as potato, tomato and eggplant and some berries popular in Brazil. As part of a program of research on pharmacologically active new molecules, the aim in this study was to assess the mutagenic effects of Solanum palinacanthum, known popularly as joá. The crude 95% ethanol extract and purified solamargine obtained from the fruits of S. palinacanthum Dunal were investigated by the Ames test, using the Salmonella typhimurium strains TA98, TA97a, TA100 and TA102 as test organisms, with and without metabolic activation. The concentrations tested ranged from 0.07 to 15.0 mg/plate for the crude ethanolic extract and from 1.25 to 5.0 mg/plate for the solamargine. The results showed a mutagenic effect of both the extract and the solamargine in the TA98 strain (without metabolic activation). The present study showed the potential mutagenicity and suggests confirming this effect in other models, before recommending their indiscriminate consumption by the population.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Low-Protein Diet during Lactation and Maternal Metabolism in Rats

Some metabolic alterations were evaluated in Wistar rats which received control or low-protein (17%; 6%) diets, from the pregnancy until the end of lactation: control non-lactating (CNL), lactating (CL), low-protein non-lactating (LPNL) and lactating (LPL) groups. Despite the increased food intake by LPL dams, both LP groups reduced protein intake and final body mass was lower in LPL. Higher serum glucose occurred in both LP groups. Lactation induced lower insulin and glucagon levels, but these were reduced by LP diet. Prolactin levels rose in lactating, but were impaired in LPL, followed by losses of mammary gland (MAG) mass and, a fall in serum leptin in lactating dams. Lipid content also reduced in MAG and gonadal white adipose tissue of lactating and, in LPL, contributed to a decreased daily milk production, and consequent impairment of body mass gain by LPL pups. Liver mass, lipid content and ATP-citrate enzyme activity were increased by lactation, but malic enzyme and lipid: glycogen ratio elevated only in LPL. Conclusion. LP diet reduced the development of MAG and prolactin secretion which compromised milk production and pups growth. Moreover, this diet enhanced the store of lipid to glycogen ratio and suggests a higher risk of fatty liver development

Effect of nutritional recovery with soybean flour diet on body composition, energy balance and serum leptin concentration in adult rats

<p>Abstract</p> <p>Background</p> <p>Malnutrition in early life is associated with obesity in adulthood and soybean products may have a beneficial effect on its prevention and treatment. This study evaluated body composition, serum leptin and energy balance in adult rats subjected to protein restriction during the intrauterine stage and lactation and recovering on a soybean flour diet.</p> <p>Methods</p> <p>Five groups of the Wistar strain of albino rats were used: CC, offspring born to and suckled by mothers fed a control diet and fed the same diet after weaning; CS, offspring born to and suckled by mothers fed a control diet and fed a soybean diet with 17% protein after weaning; LL, offspring of mothers fed a low protein diet and fed the same diet after weaning; LC, offspring of mothers fed a low protein diet, but fed a control diet after weaning; LS, offspring of mothers fed a low protein diet, but fed a soybean diet with 17% protein after weaning. Food intake, body, perirenal and retroperitoneal adipose tissue were measured in grams. Leptin was quantified using the Enzyme Linked Immuno Sorbent Assay (ELISA) and insulin by radioimmunoassay (RIA). Carcass composition was determined by chemical methods and energy expenditure was calculated by the difference between energy intake and carcass energy gain. Data were tested by analysis of variance (ANOVA).</p> <p>Results</p> <p>The LC and LS groups had higher energetic intake concerning body weight, lower energy expenditure, proportion of fat carcass and fat pads than CC and CS groups. The LS group showed reduced body weight gain and lower energy efficiency, which was reflected in less energy gain as protein and the proportion of carcass protein, and lower energy gain as lipid than in the LC groups, although both groups had eaten the same amount of diet and showed equal energy expenditure. Serum leptin did not differ among groups and was unrelated to food or energy intake and energy expenditure. Serum insulin was higher in the LS than in the LC group.</p> <p>Conclusion</p> <p>Protein restriction during intrauterine life and lactation periods did not provoke obesity in adulthood. Nutritional recovery with soybean diet decreased the body weight at the expense of lower energy efficiency with repercussion on lean mass.</p

Herbicidas na nodulação e na fixação de N2 em caupi

An experiment was carried out under greenhouse conditions in order to evaluate the effects of soil applications of different herbicides on nodulation and nitrogen fixation in cowpea [Vigna unguiculata (L.) Walp]. Treatments included a control (without herbicide) and application of the herbicides at the recommended rates and at the double of these rates (triflurarin 1.8 and 3.6 L.ha-1; EPTC 5.0 and 10.0 L.ha-1; pendimethalin 2.0 and 4.0 L.ha-1; metribuzin 1.1 and 2.2 L.ha-1; linuron 2.4 and 4.8 L.ha-1; imazaquim 1.0 and 2.0 L.ha-1). All treatments were inoculated with Bradyrhizobium, strain NBF 09. Growth of cowpea was evaluated at 20, 40, 60, and 80 days after planting. The data suggested that cowpea nodulation was affected by trifluralin (1.8 L.ha-1) linuron (2.4 L.ha-1), and imazaquim (1.0 L.ha-1), but the effects occurred only at the earlier stages of cowpea growth. Total nitrogenase activity was reduced in the soil treated with herbicides. Metribuzin and linuron showed a large degree of fitotoxicity to the crop, inhibiting its vegetative growth. Notwithstanding these effects observed on nodulation and nitrogen fixation, the herbicides seem not to have affected nitrogen uptake.Objetivando avaliar os efeitos da aplicação de distintos herbicidas na nodulação e na fixação do N2 em caupi [Vigna unguiculata (L.) Walp], foi instalado um experimento em casa de vegetação, utilizando um Latossolo Vermelho-Amarelo, da Zona da Mata Norte de Pernambuco. Os tratamentos incluíram a aplicação de herbicidas em doses correspondentes às recomendadas e ao dobro destas (trifluralin 1,8 e 3,6 L.ha-1; EPTC 5,0 e 10,0 L.ha-1; pendimethalin 2,0 e 4,0 L.ha-1; metribuzin 1,1 e 2,2 L.ha-1; linuron 2,4 e 4,8 L.ha-1; e imazaquim 1,0 e 2,0 L.ha-1), além de um tratamento sem herbicida (controle). Em todos os tratamentos as sementes de caupi (variedade BR-IPA-206) foram infectadas com a estirpe de Bradyrhizobium NFB 09. O desenvolvimento do caupi foi avaliado aos 20, 40, 60 e 80 dias após o plantio. Os resultados mostraram que a nodulação foi afetada na presença dos herbicidas trifluralin (1,8 L.ha-1), linuron (2,4 L.ha-1) e imazaquim (1,0 L.ha-1), mas os efeitos ocorreram apenas nos estádios iniciais do desenvolvimento da variedade de caupi estudada. A atividade total da enzima nitrogenase foi reduzida no solo tratado com herbicidas. O metribuzin e o linuron apresentaram elevado grau de fitotoxicidade para a cultura, inibindo o seu desenvolvimento vegetativo. Apesar dos efeitos observados na nodulação e na fixação do nitrogênio, os herbicidas não afetaram diretamente a acumulação de nitrogênio pelas plantas de caupi