The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.

Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells

Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia colicells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficientE. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

Nucleotide excision repair pathway assessment in DNA exposed to low-intensity red and infrared lasers

Low-intensity lasers are used for prevention and management of oral mucositis induced by anticancer therapy, but the effectiveness of treatment depends on the genetic characteristics of affected cells. This study evaluated the survival and induction of filamentation of Escherichia coli cells deficient in the nucleotide excision repair pathway, and the action of T4endonuclease V on plasmid DNA exposed to low-intensity red and near-infrared laser light. Cultures of wild-type (strain AB1157) E. coli and strain AB1886 (deficient in uvrA protein) were exposed to red (660 nm) and infrared (808 nm) lasers at various fluences, powers and emission modes to study bacterial survival and filamentation. Also, plasmid DNA was exposed to laser light to study DNA lesions produced in vitro by T4endonuclease V. Low-intensity lasers:i) had no effect on survival of wild-type E. coli but decreased the survival of uvrA protein-deficient cells,ii) induced bacterial filamentation, iii) did not alter the electrophoretic profile of plasmids in agarose gels, andiv) did not alter the electrophoretic profile of plasmids incubated with T4 endonuclease V. These results increase our understanding of the effects of laser light on cells with various genetic characteristics, such as xeroderma pigmentosum cells deficient in nucleotide excision pathway activity in patients with mucositis treated by low-intensity lasers.

Low-intensity red and infrared laser effects at high fluences on Escherichia coli cultures

Semiconductor laser devices are readily available and practical radiation sources providing wavelength tenability and high monochromaticity. Low-intensity red and near-infrared lasers are considered safe for use in clinical applications. However, adverse effects can occur via free radical generation, and the biological effects of these lasers from unusually high fluences or high doses have not yet been evaluated. Here, we evaluated the survival, filamentation induction and morphology of Escherichia coli cells deficient in repair of oxidative DNA lesions when exposed to low-intensity red and infrared lasers at unusually high fluences. Cultures of wild-type (AB1157), endonuclease III-deficient (JW1625-1), and endonuclease IV-deficient (JW2146-1) E. coli, in exponential and stationary growth phases, were exposed to red and infrared lasers (0, 250, 500, and 1000 J/cm2) to evaluate their survival rates, filamentation phenotype induction and cell morphologies. The results showed that low-intensity red and infrared lasers at high fluences are lethal, induce a filamentation phenotype, and alter the morphology of the E. coli cells. Low-intensity red and infrared lasers have potential to induce adverse effects on cells, whether used at unusually high fluences, or at high doses. Hence, there is a need to reinforce the importance of accurate dosimetry in therapeutic protocols.

Bone mineral density of Brazilian girls with juvenile dermatomyositis

We measured bone mineral density (BMD) in girls with juvenile dermatomyositis (JDM) considering multiple factors in order to determine if it could be used as a predictor of reduction in bone mass. A cross-sectional study of lumbar spine BMD (L2-L4) was conducted on 10 girls aged 7-16 years with JDM. A group of 20 age-matched healthy girls was used as control. Lumbar spine BMD was measured by dual-energy X-ray absorptiometry. Weight, height and pubertal Tanner stage were determined in all patients and controls. Duration of disease and mean daily and cumulative steroid doses were calculated for all patients on the basis of their medical charts. JDM activity was determined on the basis of the presence of muscle weakness, cutaneous vasculitis and/or elevation of serum concentration of one or more skeletal muscle enzymes. Seven patients demonstrated osteopenia or osteoporosis. Lumbar BMD was significantly lower in the JDM patients than the age-matched healthy control girls (0.712 vs 0.878, respectively; Student t-test, P = 0.041). No significant correlation between BMD and age, height, Tanner stage, disease duration, corticosteroid use, or disease activity was observed in JDM girls, but a correlation was observed between BMD and weight (Pearson's correlation coefficient, r = 0.802). Patients with JDM may be at risk for a significant reduction in BMD that might contribute to further skeletal fragility. Our results suggest that reduced bone mass in JDM may be related to other intrinsic mechanisms in addition to steroid treatment and some aspects of the disease itself may contribute to this condition.

Bone mineral density of the lumbar spine of Brazilian children and adolescents aged 6 to 14 years

The authors performed a study of bone mass in eutrophic Brazilian children and adolescents using dual-energy X-ray absorptiometry (DXA) in order to obtain curves for bone mineral content (BMC) and bone mineral density (BMD) by chronological age and correlate these values with weight and height. Healthy Caucasian children and adolescents, 120 boys and 135 girls, 6 to 14 years of age, residents of São Paulo, Brazil, were selected from the Pediatric Department outpatient clinic of Hospital São Paulo (Universidade Federal de São Paulo). BMC, BMD and the area of the vertebral body of the L2-L4 segment were obtained by DXA. BMC and BMD for the lumbar spine (L2-L4) presented a progressive increase between 6 and 14 years of age in both sexes, with a distribution that fitted an exponential curve. We identified an increase of mineral content in female patients older than 11 years which was maintained until 13 years of age, when a new decrease in the velocity of bone mineralization occurred. Male patients presented a period of accelerated bone mass gain after 11 years of age that was maintained until 14 years of age. At 14 years of age the mean BMD values for boys and girls were 0.984 and 1.017 g/cm², respectively. A stepwise multiple regression analysis of paired variables showed that the "vertebral area-age" pair was the most significant in the determination of BMD values and the introduction of a third variable (weight or height) did not significantly increase the correlation coefficient

Hepatitis C virus genotypes in Southern Brazil

The prevalence of hepatitis C virus (HCV) genotypes in Southern Brazil was studied in the plasma of 100 HCV-RNA-positive patients attended in Porto Alegre, South of Brazil. Reverse transcriptionpolymerase chain reaction (RT-PCR) products from the 5' noncoding region were double digested with RsaI-HaeIII and BstNI-HinfI and analyzed by restriction fragment length polymorphism (RFLP). Three genotypes (1, 2 and 3) were demonstrable, the most prevalent being HCV type 1 (55 of 100 patients, 55 per cent), followed by HCV type 3 (37 of 100 patients, 37 per cent) and HCV type 2 (8 of 100 patients, 8 per cent). There was an unusual high prevalence of genotype 3, in contrast to the majority of published data from the Southeast region.

Febre reumática: manifestaçöes articulares atípicas / Rheumatic fever: atypical articular manifestations

O diagnóstico de febre reumática (FR) continua sendo um dos mais difíceis em pediatria, devido ao polimorfismo do seu quadro e à falta de exames laboratoriais específicos ou patognomônicos da doença. Este trabalho aborda o critério diagnóstico mais freqüente e menos específico, a artrite. Foram estudadas 93 crianças (117 surtos) acompanhadas no setor de Reumatologia Pediátrica do Departamento de Pediatria da Escolar Paulista de Medicina, sendo critério de inclusäo a presença de artrite. O diagnóstico foi baseado na história clínica, exame físico e exames complementares, tendo sido considerados os critérios de Jones modificados. Em 45// observamos artrite e cardite, em 7// artrite e coréia e em 4// artrite, cardite e coréia. A artrite foi migratória em 75 surtos (64// e aditiva em 42 (32//), poliarticular em 64// e pauciarticular em 36//. Monoartrite foi encontrada em 3//. Em 5// foi observada artrite de coxofemoral como manifestaçäo inicial da doença. O tempo de duraçäo da artrite foi igual ou maior a seis semanas em 5// dos surtos. O diagnóstico definitivo de FR nos casos com manifestaçöes articulares atípicas só foi possível com a presença de cardite ou coréia. Os autores chamam a atençäo para o diagnóstico diferencial da FR com outras doenças, principalmente quando a artrite é o único critério maior encontrado

Esquistossomose aguda autoctone no municipio de Paracambi - RJ. / Autochthonous acute schistosomiasis in the municipality of Paracambi - RJ

Os autores relatam tres casos de esquistossomose mansoni aguda cujas manifestacoes clinicas surgiram 40 dias apos o provavel banho infectante, na localidade de Cascata, municipio de Paracambi, RJ. As observacoes foram feitas a partir de um caso-indice, que apresentava quadro infeccioso agudo inicialmente rotulado como salmonelose. Sao descritas as manifestacoes clinicas (febre, diarreia, rash cutaneo, esplenomegalia) e laboratoriais (leucocitose com eosinofilia significativa).Descrevem-se as caracteristicas ecologicas da area em questao, bem como a situacao do foco, de acordo com estudos realizados pela Superintendencia de Campanhas do Ministerio da Saude (SUCAM)