Abstract Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud’s arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.
Resumo O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (−1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição −1237 com psicose e anemia (p < 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p < 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.
Abstract Canine visceral leishmaniasis (CVL) caused by Leishmania (Leishmania) infantum is transmitted by phlebotomine sandflies and a major zoonotic disease in Brazil. Due to the southward expansion of the disease within the country and the central role of dogs as urban reservoirs of the parasite, we have investigated the occurrence of CVL in two municipalities Erval Velho and Herval d’Oeste in the Midwest region of Santa Catarina state. Peripheral blood samples from 126 dogs were collected in both cities and tested for anti-L. infantum antibodies by indirect enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence reaction (IIF) and for the presence of parasite DNA by polymerase chain reaction (PCR) in peripheral blood. From examined dogs, 35.71% (45/126) were positive for at least one of the three tests and two (1.6%) were positive in all performed tests. Twelve dogs (9.5%) were positive for both ELISA and IIF, while 21 dogs were exclusively positive for ELISA (16.7%), and 15 (11.9%) for IIF. L. infantum k-DNA was detected by PCR in 9 out of 126 dogs (7.1%) and clinical symptoms compatible with CVL were observed for 6 dogs. Taken together, these results indicate the transmission of CVL in this region, highlighting the needs for epidemiological surveillance and implementation of control measures for CVL transmission in this region.
Resumo A Leishmaniose Visceral Canina (LVC) causada pela Leishmania (Leishmania) infantum e transmitida por flebotomíneos e é uma das principais zoonoses do Brasil que se encontra em expansão em estados da região sul do país, sendo os cães o principal reservatório urbano do parasito. O presente estudo investigou a ocorrência de LVC em dois municípios, Erval Velho e Herval d’Oeste localizados no meio-oeste de Santa Catarina. Para tanto, amostras de sangue periférico de 126 cães foram coletadas em ambas as cidades e submetidas à detecção de anticorpos anti-L. infantum por meio de testes de ELISA e imunofluorescência indireta (IFI), bem com a detecção de k-DNA pela reação em cadeia de polimerase (PCR). Além disso, também foram observados os sintomas clínicos e as condições ambientais associadas a esses animais. Dos cães examinados, 35,7% (45/126) foram positivos para pelo menos um dos três testes, dois cães (1,6%) foram positivos em todos os três testes, 12 cães (9,5%) foram positivos tanto no ELISA quanto na IFI, enquanto 21 cães (16,7%) foram positivos para ELISA e 15 (11,9%) para o IFI. A amplificação do k-DNA de L. infantum foi positiva em 9 dos 126 cães (7,1%). Entre os cães positivos seis apresentaram um ou mais sintomas clínicos correlacionados com a LVC. Esses resultados confirmaram a ocorrência de LVC na região e destacaram a importância do monitoramento e implementação de medidas de controle para a LVC nessa região
Abstract Silicon (Si) is an element that can improve the growth and development of rice plants in water-deficient environments because it is an enzymatic stimulant, signaling for production of antioxidant compounds. Therefore, the aim of this study was to examine the relationship between water deficiency and the effect of Si on two rice cultivars whose seeds were treated with dietholate. The experimental design was fully randomized with three replicates, and treatments were organized in a 3x2x2x4 factorial arrangement: three water soil conditions (50% and 100% of soil water retention capacity (WRC) and complete submergence in a water blade of 5.0 cm); two cultivars (IRGA 424 RI and Guri INTA CL); two sources of Si (sodium metasilicate and potassium metasilicate); and four rates of Si (0; 4.0; 8.0 and 16 g L-1). Chlorophyll a and b, leaf area and shoot and root dry weight increased at higher rates of Si under the three soil water regimes. There was an increase in superoxide dismutase and guaiacol peroxidase enzyme activity in the cultivars at higher rates of Si, reducing lipid peroxidation caused by water deficiency. Therefore, Si did indeed attenuate water deficiency stress in rice plants emerging from seeds treated with dietholate.
Resumo O silício (Si) é um elemento que pode proporcionar melhor crescimento e desenvolvimento às plantas de arroz cultivadas em ambientes com deficiência hídrica, por ser um estimulador enzimático, promovendo sinalização para produção de compostos antioxidantes. Assim, o objetivo deste trabalho foi estudar a relação entre deficiência hídrica e o efeito do Si em duas cultivares de arroz tratadas com dietholate. O delineamento experimental utilizado foi inteiramente casualizado, com três repetições e os tratamentos arranjados em esquema fatorial 3x2x2x4, sendo os fatores: três condições hídricas do solo (50%, 100% da capacidade de retenção de água no solo (CRA) e lâmina d’água de 5,0 cm), duas cultivares (IRGA 424 RI e Guri INTA CL), duas fontes de Si (metassilicato de sódio e metassilicato de potássio) e quatro doses de Si (0; 4,0; 8,0 e 16 g L-1). O índice de clorofila a e b, a área foliar e o teor de massa seca da parte aérea e raiz aumentaram com o aumento das doses de Si nas três condições hídricas do solo. Houve um aumento na atividade das enzimas superóxido dismutase e guaiacol peroxidase nas cultivares estudadas à medida que as doses de Si aumentaram, diminuindo a peroxidação de lipídios, causada pela restrição hídrica. Portanto, o Si atenua o estresse por déficit hídrico em plantas de arroz emergentes de sementes tratadas com dietholate.
Abstract Multiphasic calcium phosphate powders were synthesized by the acidic route, using lactic acid as a chelating agent that allows the production of a stable and rich solution of calcium and phosphate ions at room temperature. After pH adjusting, without varying the concentrations of precursor solution, XRD and FTIR analyses showed different CaP phases before and after heat treatment at 1000 °C. At pH 5, brushite plate-like particles were produced, while at higher pH levels (7 to 12) nano-hydroxyapatite particles were formed. After the calcination process, partial and total decomposition of hydroxyapatite in the β-TCP phase was explained by XRF analysis due to the calcium-deficient hydroxyapatite of synthesized samples at pH 7 and 10. This work presents an important method to synthesize any desired CaP phase compositions by varying the pH level and subsequently performing heat treatment, which has a direct effect on morphology, crystallinity, and formation of different CaP powders.
Abstract Objective: To describe fluid resuscitation practices in Brazilian intensive care units and to compare them with those of other countries participating in the Fluid-TRIPS. Methods: This was a prospective, international, cross-sectional, observational study in a convenience sample of intensive care units in 27 countries (including Brazil) using the Fluid-TRIPS database compiled in 2014. We described the patterns of fluid resuscitation use in Brazil compared with those in other countries and identified the factors associated with fluid choice. Results: On the study day, 3,214 patients in Brazil and 3,493 patients in other countries were included, of whom 16.1% and 26.8% (p < 0.001) received fluids, respectively. The main indication for fluid resuscitation was impaired perfusion and/or low cardiac output (Brazil: 71.7% versus other countries: 56.4%, p < 0.001). In Brazil, the percentage of patients receiving crystalloid solutions was higher (97.7% versus 76.8%, p < 0.001), and 0.9% sodium chloride was the most commonly used crystalloid (62.5% versus 27.1%, p < 0.001). The multivariable analysis suggested that the albumin levels were associated with the use of both crystalloids and colloids, whereas the type of fluid prescriber was associated with crystalloid use only. Conclusion: Our results suggest that crystalloids are more frequently used than colloids for fluid resuscitation in Brazil, and this discrepancy in frequencies is higher than that in other countries. Sodium chloride (0.9%) was the crystalloid most commonly prescribed. Serum albumin levels and the type of fluid prescriber were the factors associated with the choice of crystalloids or colloids for fluid resuscitation.
RESUMO Objetivo: Descrever as práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras e compará-las com as de outros países participantes do estudo Fluid-TRIPS. Métodos: Este foi um estudo observacional transversal, prospectivo e internacional, de uma amostra de conveniência de unidades de terapia intensiva de 27 países (inclusive o Brasil), com utilização da base de dados Fluid-TRIPS compilada em 2014. Descrevemos os padrões de ressuscitação volêmica utilizados no Brasil em comparação com os de outros países e identificamos os fatores associados com a escolha dos fluidos. Resultados: No dia do estudo, foram incluídos 3.214 pacientes do Brasil e 3.493 pacientes de outros países, dos quais, respectivamente, 16,1% e 26,8% (p < 0,001) receberam fluidos. A principal indicação para ressuscitação volêmica foi comprometimento da perfusão e/ou baixo débito cardíaco (Brasil 71,7% versus outros países 56,4%; p < 0,001). No Brasil, a percentagem de pacientes que receberam soluções cristaloides foi mais elevada (97,7% versus 76,8%; p < 0,001), e solução de cloreto de sódio a 0,9% foi o cristaloide mais comumente utilizado (62,5% versus 27,1%; p < 0,001). A análise multivariada sugeriu que os níveis de albumina se associaram com o uso tanto de cristaloides quanto de coloides, enquanto o tipo de prescritor dos fluidos se associou apenas com o uso de cristaloides. Conclusão: Nossos resultados sugerem que cristaloides são usados mais frequentemente do que coloides para ressuscitação no Brasil, e essa discrepância, em termos de frequências, é mais elevada do que em outros países. A solução de cloreto de sódio 0,9% foi o cristaloide mais frequentemente prescrito. Os níveis de albumina sérica e o tipo de prescritor de fluidos foram os fatores associados com a escolha de cristaloides ou coloides para a prescrição de fluidos.
Abstract The objective of this study was to characterize and compare the hematological variables (erythrogram, thrombogram, leukogram and plasma metabolites) of three cichlid species: Cichla monoculus, Cichla temensis and Cichla vazzoleri. A total of 45 specimens were captured in Balbina lake, Presidente Figueiredo, Amazonas, Brazil, with the aid of a rod and reel or hand line, with natural or artificial bait: 15 C. monoculus, 15 C. temensis and 15 C. vazzoleri. Their blood was removed by means of caudal puncture of the dorsal aorta, and hematological data were determined in accordance with methodology previously described in the literature. The erythrogram showed similarities between the species, while the thrombogram showed differences between C. vazzoleri and the other species studied (C. monoculus and C. temensis). The total leukocyte counts for C. temensis and C. vazzoleri were higher than those of C. monoculus. The predominant leukocyte in C. temensis and C. vazzoleri was lymphocytes, whereas it was monocytes in C. monoculus. The plasma metabolites showed differences between the three cichlid species, regarding their glucose, cholesterol, urea and potassium levels. It is concluded that these three species present hematological differentiation, thus indicating that they have differentiated blood-cell immune responses and plasma metabolite physiology.
Resumo O presente trabalho teve por objetivo caracterizar e comparar as variáveis hematológicas (eritrograma, trombograma, leucograma e metabólitos plasmáticos) de três espécies de tucunarés Cichla monoculus, Cichla temensis e Cichla vazzoleri. Um total de 45 animais foi capturado no lago de Balbina, Presidente Figueiredo, Amazonas, com auxílio de vara e carretilha, linha de mão com isca natural e artificial, sendo 15 C. monoculos, 15 C. temensis e 15 C. vazzoleri. O sangue foi retirado por punção caudal da aorta dorsal e os dados hematológicos foram determinados de acordo com metodologia previamente descrita na literatura. No eritrograma foram observadas similaridades entre as espécies, o trombograma demonstrou diferenças entre o C. vazzoleri e as demais espécies estudadas (C. monoculus e C. temensis), a contagem total de leucócitos demonstrou que em C. temensis e C. vazzoleri os valores são superiores ao C. monoculus. Foi demonstrado que os linfócitos foram às células predominantes em C. temensis e C. vazzoleri, diferentemente do C. monoculos que apresentou como leucócito predominante os monócitos. Nos metabólitos plasmáticos, foi possível observar diferenças entre as três espécies de tucunarés nos níveis de glicose, colesterol, uréia e potássio. Conclui-se que as três espécies de tucunarés apresentam diferenciação hematológica, indicando que as mesmas possuem respostas diferenciadas, na resposta imunológica de suas células do sangue e na fisiologia dos metabólitos plasmáticos.
Abstract In this paper we present an overview of the abstracts, scientific and social programs, field trips, and achievements in terms of participant number, represented countries, sponsorships, and themes treated during the Sixth International Conference on the Comparative Biology of Monocotyledons that took place in Natal, Brazil, October 7th -12th 2018. Some comments received by the organizers and a few suggestions for organizers of the next meeting, in Costa Rica, are also provided. The conference’s complete abstract book was published and provide additional information.
Resumo Neste artigo nós apresentamos uma visão geral dos resumos, programação científica e social, viagens de campo e informações acerca do número de inscritos, países participantes, patrocínios e temas tratados durante a Sexta Conferência Internacional sobre Biologia Comparada de Monocotiledôneas, realizada em Natal, Brasil, de 7 a 12 de outubro de 2018. Alguns comentários recebidos pelos organizadores e sugestões para os organizadores do próximo Monocots, na Costa Rica, também são fornecidos. Este artigo complementa os dados publicados no livro de resumos, disponível no Repositório Digital da UFRN.
Abstract: Introduction: Cystic nephroma is a rare benign renal tumor of uncertain etiology. In children, it can manifest as a palpable abdominal mass, hematuria, and recurrent urinary infections. Imaging tests such as ultra sound and computed tomography assist in the diagnosis, but confirmation is made through anatomopathological study. Treatment is surgical and may be partial or total nephrectomy, with a good prognosis. Objective: To report a rare case of pediatric cystic nephroma, its clinical manifestations, radiological and histopathological aspects, as well as the treatment used and its evolution. Clinical Case: Pre-school, male, with a history of recurrent urinary infections in the first year of life. At 2 years and 8 months, he presented nodulation in the right hypochondrium with local pain on palpation, associated with urinary disorders and hematuria. An ultrasonography showing enlarged right kidney due to multiseptated cystic formation. Computed tomography showing multiloculated cystic expan sive formation in the right kidney. At 2 years and 10 months, he underwent partial right nephrec tomy for excision and anatomopathological study, which was compatible with Cystic Nephroma. He evolved with regression of hematuria and recurrent episodes of urinary infections, maintaining renal function preserved. Currently, at 4 years and 6 months, asymptomatic. Conclusions: Cystic nephro ma is a rare entity, generally with a good prognosis. The association of clinical findings, radiological images, and anatomopathological study are fundamental for the establishment of diagnosis and a better definition of therapeutic conduct.
Resumen: Introducción: El nefroma quístico es un tumor renal benigno raro, de etiología incierta. En niños puede manifes tarse como una masa abdominal palpable, hematuria e infecciones urinarias recurrentes. Exámenes de imagen como ultrasonografía y tomografía computadorizada ayudan en el diagnóstico, sin embar go, la confirmación se realiza mediante el estudio anatomopatológico. El tratamiento es quirúrgico, pudiendo ser nefrectomía parcial o total, con buen diagnóstico. Objetivo: Describir un caso raro de nefroma quístico pediátrico, sus manifestaciones clínicas, aspectos radiológicos e histopatológicos, así como tratamiento y su evolución. Caso Clínico: Preescolar, sexo masculino, con historia clínica de infecciones urinarias de repetición en el primer año de vida. A los 2 años y 8 meses, presentó nodulación en hipocondrio derecho con dolor local a la palpación, asociado a molestias disúricas y hematuria. La ecografía mostró un riñón derecho aumentado de volumen por formación quística multiseptada. La tomografía computadorizada demostró formación expansiva quística multioculada en el riñón derecho. A los 2 años y 10 meses, realizó nefrectomía parcial derecha para exéresis y estudio anatomopatológico, compatible con nefroma quístico. Evolucionó con regresión de la hema turia y de los episodios recurrentes de infecciones urinarias, manteniendo función renal preservada. Actualmente, con 4 años y 6 meses, asintomático. Conclusiones: El nefroma quístico es una entidad rara, en general de buen pronóstico. La asociación de hallazgos clínicos, imágenes radiológicas y es tudio anatomopatológico son fundamentales para el establecimiento diagnóstico y mejor definición de la conducta terapéutica.
Rosemary (Rosmarinus officinalis L.) is known for its bioactive compounds with high antioxidant potential and pharmacological properties, such as antibacterial, antidepressant and anti-inflammatory. These properties are attributed to the presence of (poly)phenolic compounds. In the literature there is no extraction of these compounds with a totally non-toxic solvent, capable of applying the extract directly to the food. This work aimed to optimize the extraction conditions of bioactive compounds from the rosemary leaves using water as solvent. According to the analysis of variance parameters, a cubic model of high order of significance was obtained with adjusted R2 (R squared) > 0.947. The optimal conditions of the antioxidant potential for conventional and ultrasonic agitation were: temperature 70 °C, 30 min of extraction and the solvent/solute ratio of 25, resulting in an antioxidant potential of 6861 and 7126 µmol L−1 Trolox, respectively. The electrospray ionization mass spectrometry (ESI(−)-MS/MS) analysis showed the presence of antioxidant compounds such as: carnosol (m/z 329.20), rosmanol (m/z 345.03) and rosmarinic (m/z359.14) acids. The response surface methodology evaluated the influence of the main parameters of the bioactive compounds extraction from rosemary using only water as solvent, in addition to the use of less time and sample mass, resulting in lower cost.
Micelles have aroused interest due to their ability to assist in the transport of poorly soluble drugs. In this study the mixture of copolymers F127/E45S8 in different proportions (F/ES 30/70, 50/50 and 70/30) was performed to improve the bioavailability of griseofulvin and quercetin. The results of cytotoxicity (MTT assay) revealed that the copolymers F127 and E45S8 had considerable biocompatibility and did not affect the metabolism of human neutrophils. The binary systems were also evaluated by critical micellar concentration (CMC) and thermoresponsive behavior. The CMC values were intermediate to those of the isolated copolymers. The systems maintained the thermoresponsive properties present in F127 making the systems interesting for subcutaneous administration. The systems presented small size, an average range in size from 17 to 38 nm, and the samples prepared with higher hydrophobic proportion presented more uniform sizes. Results suggest stability and the increasing of the nanosystems circulation time. The F/ES 30/70 system has polydispersity smaller than 0.1 and showed an increase of 129 times for quercetin solubility. Thus, it is possible to consider F127/E45S8 micelles as potential nanosystems for poorly soluble drug delivery.
Abstract Twenty-three hydrocarbon-degrading bacteria strains were isolated from gas station leaking-contaminated groundwater located in the Southern Amazon, Brazil. Based on hydrocarbon (diesel, hexadecane, benzene, toluene and xylene) degradation ability, two strains were selected for further study. The amplification and sequencing of the 16S rRNA gene showed that these two strains belonged to the genus Bacillus (Bacillus sp. L26 and Bacillus sp. L30). GC-MS analysis showed that strain L30 was the most effective in degrading n-alkane (C10-C27) from diesel after 7 days of cultivation in mineral medium. Both strains produced biosurfactants and showed emulsification activity, specially the strain L30. Alkane hydroxylase gene (group III), which is important for alkane biodegradation, was present in strains. As a result, this study indicated that these bacteria could have promising applications in hydrocarbon bioremediation.
Resumo Vinte e três linhagens bacterianas degradadoras de hidrocarbonetos foram isoladas de água subterrânea contaminada por vazamento em posto de combustível no sul da Amazônia, Brasil. Com base na habilidade de degradar hidrocarbonetos (diesel, hexadecano, benzeno, tolueno e xileno), duas linhagens foram selecionadas para estudos posteriores. A amplificação e sequenciamento do gene 16S rRNA demonstrou que essas linhagens pertencem ao gênero Bacillus (Bacillus sp. L26 and Bacillus sp. L30). Análises de GC-MS mostraram que a linhagem L30 foi mais eficiente em degradar n-alcanos (C10-C27) presentes no diesel, após 7 dias de cultivo em meio mineral. Ambas as linhagens produziram biossurfactantes e apresentaram atividade emulsificante, especialmente a linhagem L30. O gene alcano hidroxilase (grupo III), o qual é importante para degradação de alcanos, foram detectados nas linhagens. Como resultado, este estudo indicou que essas linhagens bacterianas podem ser promissoras se aplicadas em processos de biorremediação.
The insertion of functional groups in polymer compounds may facilitate their interaction with different drugs. PEG polymers are widely used for their low melting point, low toxicity, drug compatibility, and hydrophilicity. They are used as pharmaceutical excipients for the formulation of conventional or modified released drugs and are designed to be upgraded as drug-modulating controllers at specific sites in the body. Indomethacin has been used in the controlled release of drugs because it is a drug that have good interaction with different polymers. The drug is a non-steroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis, osteoarthritis, spondylitis, and other disorders. In this work, PEG 4000 had its chain modified by organic reactions and their derivatives were emulsified to form microparticles using polyvinyl alcohol as an emulsifier. Posteriorly were also incorporated with indomethacin. The samples were characterized to prove the influence of indomethacin on the morphology and thermal behavior of this polymer. The controlled release was performed in the time from 0 to 240 min using the Ultraviolet Spectroscopy to quantify indomethacin released from the polymer matrix for these 4 hours. Releases over the time were satisfactory as concentrations increased over time, which we can conclude that the structural modification of PEG 4000 was beneficial in the release of the indomethacin drug.
Silver nanoparticles (AgNPs) stabilized with glutathione (GSH) were used as nanosensors for the determination of fluoroquinolones such as ciprofloxacin (CIP), norfloxacin (NOR) and enrofloxacin (ENRO) in aqueous systems. The AgNPs were stabilized with GSH (Ag-GSH NPs), whereas the decrease of the surface plasmon resonance (SPR) band at 400 nm and the bathochromic shift of the absorption band were monitored. The method was validated and the analytical performance was verified. The results were satisfactory, with recoveries between 83.7 and 110% in almost all the experimental conditions and the repeatability and intermediate accuracy of less than 20%. The limits of detection were 0.397, 0.437 and 0.398 µmol L-1, and the limits of quantification were 1.203, 1.323 and 1.205 µmol L-1 for ciprofloxacin, norfloxacin and enrofloxacin, respectively. The method was selective in a group of drugs and applied in the determination of fluoroquinolones in potable water samples.
A one-pot diastereoselective synthesis of thiazolidine-ring fused systems derived from enantiomerically pure amino acids, L-cysteine or D-penicillamine, and achiral succindialdehyde is described as an experiment to be carried out by upper-division undergraduate students in a laboratory classroom. Reactions were performed under mild conditions, the products were isolated through simple experimental procedures and fully characterized. This study combines organic synthesis, determination of the purity of compounds (TLC analysis and melting point measurements), optical activity measurements as well as structural analysis (interpretation of 1D NMR and 2D NMR spectra). It offers a platform for the discussion of important organic chemistry concepts such as diastereoselectivity, kinetic control vs thermodynamic control and cyclization reactions via nucleophilic addition to imines/iminium cations.
Abstract Early age acute leukemia (EAL) shows a high frequency of KMT2A-rearrangements (KMT2A-r). Previous investigations highlighted double-strand breaks arising from maternal exposure to xenobiotics during pregnancy as a risk factor for EAL and KMT2A-r. In this case-control study, we investigated the relationship between EAL and genetic variants of the nonhomologous end-joining (XRCC6 rs5751129, XRCC4 rs6869366 and rs28360071), since they might affect DNA repair capacity, leading to KMT2A-r and leukemogenesis. Samples from 577 individuals (acute lymphoblastic leukemia-ALL, n=164; acute myeloid leukemia-AML, n=113; controls, n=300) were genotyped. No significant association was found for rs5751129 and rs6869366, whereas rs28360071 was associated with an increased risk for ALL with KMT2A-r (IIxID: OR - Odds ratio 2.23, CI 1.17-4.25, p=0.014). Bone marrow samples from ALL patients showed a higher expression of XRCC4 compared to AML patients (p=0.025). Human Splicing Finder 3.1 predicted that the deleted allele of rs28360071 is potentially associated with the activation of a 5’ cryptic splice site in intron 3 of XRCC4. The sequencing of cDNA did not show any differences on the splicing process for the rs28360071 genotypes. Our results suggest that the deleted allele for rs28360071 increases the risk for ALL with KMT2A-r, but not by modifying the XRCC4 expression levels or its structure.