Ergosterol peroxide (EP) has been extensively studied for its antitumor activities. However, its further development has been restricted due to its limited intracellular accumulation and poor aqueous solubility. In this study, a novel triphenylphosphonium cation (TPP+) moiety was coupled to ergosterol peroxide to precisely target it at tumor cell mitochondria. The synthesized Mito-EP derivatives Mito-EP-3a-3d displayed stronger cytotoxicity than the EP parent and exhibited selectively cytotoxic effects between cancer cells and normal gastric epithelial (GES-1) cells. The most potent compound, Mito-EP-3b, was 9.7-fold more efficacious than ergosterol peroxide in the MCF-7 (breast cancer) cell line and showed good selectivity (SI = IC50GES-1/IC50MCF-7 = 4.04, IC50: concentrations to inhibit 50% of cell growth). Furthermore, Mito-EP-3b was able to decrease the mitochondrial membrane potential and induced reactive oxygen species production, accompanied by activating the expression of cytochrome c and Bax, while Bcl-2 expression was suppressed. The molecular mechanism may refer to the mitochondrial apoptotic pathway. Overall, the above results incentivize the further study of Mito EP-3b derivatives as potent anticancer agents.

A series of novel betulin-28-hydrazone derivatives (7a-7o) were synthesized. All compounds were evaluated for their in vitro cytotoxicities in four human carcinoma cells (HepG2, MCF-7, HCT-116 and A549). Among them, compound 7l displayed the most potent cytotoxicity with an IC50 (concentration of the tested compound that inhibits 50% of cell growth) value of 7.37 ± 0.38 μM against MCF-7 cells. The preliminary cellular mechanism studies indicated that compound 7l could induce MCF-7 cells apoptosis. The above findings indicated that compound 7l may be used as a lead compound for antitumor agents with improved efficacy.

RESUMO O uso da temperatura como traçador natural em hidrologia é observado desde a década de 1960. Nos últimos anos, foi possível observar um resgate do uso desta propriedade física na investigação do ciclo da água. As principais razões são a redução de custos na medição de temperatura e o desenvolvimento da medição de temperatura distribuída. A partir deste contexto, este trabalho apresenta um estudo da interação rio-aquífero, na Bacia do Ribeirão da Onça (afloramento do Sistema Aquífero Guarani), a partir do uso de dados de vazão do curso principal e utilizando a temperatura como traçador natural. Duas calhas Parshall foram instaladas a uma distância de 1,2 km entre si, de forma a quantificar a vazão do curso principal e determinar a contribuição de água subterrânea. Um cabo de fibra ótica foi empregado para identificar regiões de contribuição da água subterrânea ao curso superficial, assim como uma sonda de temperatura, com termistores, foi utilizada para medir o gradiente de temperatura vertical e estimar as taxas de troca entre estes meios. Os resultados indicam uma diferença de vazão de ~250 m3.h-1 entre as calhas, o que pode ser interpretado como contribuição do fluxo de base ao rio. O sistema de medição distribuído de temperatura (DTS) permitiu a identificação de regiões de contribuição de água subterrânea, em virtude da diferença de temperatura entre água subterrânea e superficial. Taxas de descarga de 200 a 300 mm.dia-1 foram obtidas a partir das medições pontuais de temperatura, que concordam com os valores obtidos a partir da medição de vazão. O trabalho demonstra que a temperatura pode ser utilizada como um traçador natural, mesmo em áreas tropicais, em que a temperatura da água subterrânea é superior à da água superficial, especialmente nos períodos de inverno.

ABSTRACT The use of temperature as a natural tracer in hydrology is noticed since the 1960s. In recent years, there has been a revival of the use of this physical property in the investigation of water cycle. The main reasons are the cost reduction of temperature measurements and the development of distributed temperature sensing. Here, we present a study of the groundwater-surface water interaction in the Onça Creek Watershed (Guarani Aquifer System outcrop) using stream discharge data and temperature as a natural tracer. Two Parshall flumes were installed 1.2 km apart to quantify stream discharge and determine groundwater contribution. We used an optic fiber cable to identify interaction locations and a probe with thermistors to measure the vertical temperature gradient and estimate flux rates. The results show a discharge difference of ~250 m3.h-1 between both flumes, which we interpret as baseflow contribution. The distributed temperature sensing allowed the identification of regions with gaining behavior. Discharge rates between 200 and 300 mm.day-1 were determined from vertical temperature measurements, which agrees with the streamflow data. The study demonstrated that temperature is attractive as natural tracer in tropical conditions, where the groundwater temperature is higher than the surface water temperature, especially during the winter.

Abstract Total spikelet number per spike (TSS) is one of the key components of grain yield in wheat. Chromosome (chr.) 2D contains numerous genes that control TSS. In this study, we evaluated 138 F8 recombinant inbred lines (RILs) derived from an F2 population of a synthetic hexaploid wheat line (SHW-L1) and a common wheat cultivar (Chuanmai 32) for TSS in six different environments. To identify quantitative trait loci (QTL) for TSS, we constructed an integrated high-density genetic map of chr. 2D containing two simple sequence repeats, 35 diversity array technology markers, and 143 single nucleotide polymorphisms. We identified three stable QTL for TSS that individually explained 9.7–19.2% of the phenotypic variation and predicted 23 putative candidate genes within the QTL mapping interval. Overall, our results provide insight into the genetic basis of TSS in synthetic hexaploid wheat that may be useful in breeding high-yielding wheat cultivars.

Abstract Pre-harvest sprouting (PHS) is a major abiotic factor affecting grain weight and quality, and is caused by an early break in seed dormancy. Association mapping (AM) is used to detect correlations between phenotypes and genotypes based on linkage disequilibrium (LD) in wheat breeding programs. We evaluated seed dormancy in 80 Chinese wheat founder parents in five environments and performed a genome-wide association study using 6,057 markers, including 93 simple sequence repeat (SSR), 1,472 diversity array technology (DArT), and 4,492 single nucleotide polymorphism (SNP) markers. The general linear model (GLM) and the mixed linear model (MLM) were used in this study, and two significant markers (tPt-7980 and wPt-6457) were identified. Both markers were located on Chromosome 1B, with wPt-6457 having been identified in a previously reported chromosomal position. The significantly associated loci contain essential information for cloning genes related to resistance to PHS and can be used in wheat breeding programs.

Abstract The D-genome progenitor of wheat (Triticum aestivum), Aegilops tauschii, possesses numerous genes for resistance to abiotic stresses, including drought. Therefore, information on the genetic architecture of A. tauschii can aid the development of drought-resistant wheat varieties. Here, we evaluated 13 traits in 373 A. tauschii accessions grown under normal and polyethylene glycol-simulated drought stress conditions and performed a genome-wide association study using 7,185 single nucleotide polymorphism (SNP) markers. We identified 208 and 28 SNPs associated with all traits using the general linear model and mixed linear model, respectively, while both models detected 25 significant SNPs with genome-wide distribution. Public database searches revealed several candidate/flanking genes related to drought resistance that were grouped into three categories according to the type of encoded protein (enzyme, storage protein, and drought-induced protein). This study provided essential information for SNPs and genes related to drought resistance in A. tauschii and wheat, and represents a foundation for breeding drought-resistant wheat cultivars using marker-assisted selection.

SSRs have proved to be the most powerful tool for variety identification in groundnut of similar origin, and have much potential in genetic and breeding studies. To facilitate SSR discovery in groundnut, we proposed a highly simplified SSR isolation protocol based on multiple enzyme digestion/ligation, mixed biotin-labeled probes and streptavidin coated magnetic beads hybridization capture strategy. Of the 272 colonies randomly picked for sequencing, 119 were found to have unique SSR inserts

O aumento da cifose toracolombar após tratamento conservador da fratura tipo explosão é complicação constatada por vários autores. Realizamos estudo retrospectivo com 33 portadores de fratura toracolombar do tipo explosão submetidos ao tratamento conservador entre 1992 a 2004 para verificar a correlação entre a cifose toracolombar e a Classificação de McCormack, que pontua a gravidade da fratura conforme a cominuição do corpo, o deslocamento dos fragmentos no corpo vertebral e a quantidade de correção da deformidade em cifose após o tratamento. Após 30 meses de seguimento médio, verificamos correlação entre a pontuação da Classificação de McCormack, conhecida na literatura como load sharing classification, e o colapso vertebral sagital nestes pacientes (p<0,05;r=0,65). A despeito de ser descrita para avaliação do colapso sagital após o tratamento cirúrgico, a aplicabilidade desta Classificação pode ser considerada para os portadores de fratura toracolombar explosão submetidos ao tratamento conservador.

The increasing incidence of thoracolumbar kyphosis after conservative treatment of burst fractures is a complication reported by several authors. We performed a retrospective study on a consecutive series of 33 patients with thoracolumbar burst fractures treated with cast or brace immobilization between 1992 and 2004 to check for a correlation between thoracolumbar kyphosis and Load Sharing Classification, which provides fracture severity scores according to body comminution, vertebral body fragments displacement and the amount of kyphosis correction delivered after treatment. After an average of 30 months of follow-up we found a correlation between Load Sharing Classification scores (also known as McCormack's Classification), and the sagittal kyphotic deformity on these patients (p<0.05;r=0.65). Despite of being described for assessing sagittal deformity after surgical treatment, the applicability of this Classification can be considered for patients with thoracolumbar burst fractures submitted to conservative treatment.

OBJETIVO: Os autores discutem a correlação existente entre a cifose torácica aumentada, em pacientes portadores de Dorso Curvo Postural (DCP) ou Doença de Scheuermann (DS), e a contratura dos músculos isquiotibiais. Esta relação é pouco estudada na literatura. MÉTODOS: No período de junho a dezembro de 2003, foram analisados 38 pacientes. Dentre os pacientes, 26 (68,4 %) eram do sexo masculino e 12 (31,6%) do sexo feminino. A idade mínima foi de 10 anos e a máxima de 20 anos, com média de 15,36. Encontramos 20 (52,6%) pacientes portadores de Doença de Scheuermann e 18 (47,4%) com Dorso Curvo Postural. RESULTADOS: De todos os 38 pacientes estudados, 32 (84,2%) apresentaram contratura dos isquiotibiais, o que foi estatisticamente significante (p<0,001). Analisando apenas pacientes com DS encontramos 85% de contratura e 83,3% nos com DCP. CONCLUSÃO: Não houve diferença estatística, da porcentagem de contratura dos isquiotibiais na DS em relação ao DCP (p=0,61).

OBJECTIVE: The authors discuss the existent correlation between augmented thoracic kyphosis in patients with juvenile Kyphosis or Scheuermann`s disease and hamstrings contraction. This correlation is marginally addressed by existing studies. METHODS: Between June and December 2003, 38 patients belonging to the Spine Group at the Department of Orthopaedics from Santa Casa de São Paulo, Brazil, were analyzed. Among them, 26 (68.4%) were males and 12 (81.6%) were females. The youngest age was 10 and the oldest one was 20 years, with an average of 15.36. Twenty (52.6%) patients presented with Scheuermann´s disease and 18 (47.4%) with juvenile Kyphosis. RESULTS: From all 38 patients under study, 32 (84.2%) presented hamstring contracture, which was statistically significant (p<0.001). 85% of patients presenting only Scheuermann`s disease and 83.3% of patients with only juvenile Kyphosis had contracture. Conclusion: There was no statistically significant difference between contraction percentage in Scheuermann`s disease patients versus juvenile Kyphosis patients (p=0.61).

OBJETIVO: Foram avaliados retrospectivamente nove casos de discite na infância, confirmando suas formas variadas de apresentação, que levam ao atraso e dificuldades no diagnóstico. MÉTODOS: Os autores demonstraram que as radiografias iniciais podem se apresentar sem alterações, sendo importantes os exames de cintilografia ou ressonância magnética, nesses casos. RESULTADOS E CONSLUSÕES: Um paciente necessitou de tratamento cirúrgico para descompressão do canal lombar, devido à presença de abscesso discal. Os demais pacientes foram tratados conservadoramente, através de repouso, antibioticoterapia adequada e imobilização. Todos os pacientes evoluíram satisfatoriamente, e não apresentavam queixas nas suas avaliações finais.

BACKGROUND: The authors reviewed nine patients presenting with discitis during infancy, demonstrating that its diverse forms of presentation lead to a delayed and difficult diagnosis. METHODS: This study reports that initial radiographs may not show any alterations, enhancing the importance of scintillography or magnetic resonance for these cases. RESULTS AND CONCLUSIONS: One patient was submitted to surgical treatment for lumbar canal decompression due to the presence of a disk abscess. The remaining patients were treated conservatively only with an appropriate antibiotic therapy, immobilization and restriction of physical activity. All of the young patients had a satisfactory evolution and stated no complaints about sequels during their final evaluation.

CONTEXTO: O fibrohistiocitoma benigno intra-ósseo é uma neoplasia rara, caracterizada por proliferação fibroblástica e fibras colágenas. A dor na região lombar é uma queixa freqüente em muitos pacientes, mas, na maioria das vezes está relacionada com causa muscular ou degenerativa. RELATO DE CASO: Relata-se aqui o caso de um paciente com diagnóstico de fibrohistiocitoma benigno ósseo na coluna lombar que apresentava queixa de lombalgia há cinco meses antes do diagnóstico. Foi submetida à biópsia aberta transpedicular na quarta vértebra lombar ,e, posteriormente realizada curetagem da lesão via anterior retroperitonial e artrodese vertebral de L3-L5 com enxerto de fíbula. CONCLUSÃO: Apesar de raro, o fibrohistiocitoma benigno intra-ósseo deve ser uma das hipóteses quando observamos uma lesão primária na coluna vertebral.

CONTEXT: Benign intraosseous fibrous histiocytoma is a rare neoplasia, characterized by fibroblastic and collagenous fiber proliferation. Pain in the lumbar region is a frequent complaint in many patients, but most of times it is associated to muscular or degenerative causes. CASE REPORT: Here we report a case of a patient diagnosed with benign bone fibrous histiocytoma in the lumbar spine who complained of lumbar pain dating five months prior to diagnosis. The patient was submitted to open transpedicular biopsy in the forth lumbar vertebra, and subsequently, lesion curettage was performed via anterior retroperitoneal and L3-L5 vertebral arthrodesis using a fibular graft. CONCLUSION: Although rare, benign intraosseous fibrohistiocytoma should be taken into consideration when a primary lesion is observed in the spine.

A instabilidade lombar é uma doença freqüente na prática clínica. Vários autores preconizam o uso de parafusos pediculares para fixação da artrodese posterior, demonstrando melhores resultados do que a estabilização in situ. OBJETIVO: Avaliar o resultado funcional e radiográfico dos pacientes que procuraram o Grupo de Coluna da Faculdade de Ciências Médicas da Santa Casa de São Paulo portadores de instabilidade lombar submetidos ao tratamento cirúrgico pela artrodese vertebral por via posterior utilizando-se fixação metálica representada por parafusos pediculares. MÉTODOS: Foram coletados dados dos prontuários médicos do Serviço de Arquivos Médicos (S.A.M.E) da Irmandade da Santa Casa de Misericórdia de São Paulo e avaliação por meio de radiografias simples nas incidências frente, perfil e oblíquas para estudos de imagem além da avaliação funcional pré e pós-operatória, com seguimento mínimo de dois anos. RESULTADOS: Durante o período de Novembro de 1995 à Junho de 2000 avaliamos dez pacientes portadores de instabilidade lombar degenerativa (48%), cinco pacientes com espondilolistese ístmica (23%) e seis com estenose lombar degenerativa (29%). Quanto à avaliação funcional, obtivemos 76% de resultados excelentes e bons. As complicações verificadas foram infecção superficial, pseudartrose e posicionamento inadequado dos parafusos (19%). CONCLUSÕES: Os autores concluem que este método de fixação é eficaz, apresentando fusão da artrodese em 95% dos pacientes.

The lumbar instability is a common desease in clinical practice. Several authors recommend the use of pedicular screws as a fixation system for posterior arthodesis since they provide better results compared to in situ stabilization. Objective: to evaluate the functional and radiographic results in patients assisted by the Spine Group of the Medical Sciences School of Santa Casa of São Paulo, presenting lumbar instability and who underwent posterior vertebral arthrodesis treatment by using melttalic fixation with pedicular screws. METHODS: Data from medical records of the Service of Medical Files (S.A.M.E) of the Irmandade da Santa Casa de Misericórdia de São Paulo and evaluation through single radiographs (front, lateral, and oblique sections) for image studies besides a pre- and postoperative functional evaluation, with minimal follow-up of two years. RESULTS: From November 1995 to June 2000 ten patients with degenerative lumbar unstableness (48%), five patients with isthmic spondylolisthesis (23%) and six with degenerative lumbar stenosis (29%) were evaluated. As for functional evaluation, excellent and good results were obtained in 76%. Complications included superficial infection, pseudoarthrosis, and inappropriate positioning of screws (19%). CONCLUSIONS: The authors conclude that this fixation method is effective with arthrodesis fusion seen in 95% of patients.