Tradução e validação para a língua portuguesa da escala de graduação da síndrome das pernas inquietas do Grupo Internacional do Estudo da Síndrome das Pernas Inquietas

BACKGROUND: Restless legs syndrome (RLS) is a chronic sensory-motor disorder characterized by unpleasant limb sensations and an irresistible urge to move. The International Restless Legs Syndrome Study Group developed the Restless Legs Syndrome Rating Scale (IRLS) to assess the severity of RLS symptoms. The objective of this study was to translate and validate the IRLS into Brazilian Portuguese. METHOD: The IRLS was translated into Brazilian Portuguese, analyzed, back translated to English, and compared to the original version. It was applied to 10 patients for cultural verification. The language was adjusted and the final version was administered to 30 patients (13 male, mean age 58.88±14.82). RESULTS: There was correlation among the IRLS evaluation of three experts. Many linguistic adaptations were required to achieve cultural adequacy and the Cronbach's alpha coefficient showed reliability of 80%. CONCLUSION: IRLS was translated, adapted, and validated to Brazilian Portuguese language, showing good reliability and validity.INTRODUÇÃO: A síndrome das pernas inquietas (SPI) é uma doença crônica, sensório-motora, caracterizada por sensações desagradáveis nos membros e uma urgência em movimentá-los. O Grupo Internacional de Estudos da Síndrome das Pernas Inquietas desenvolveu a Escala de Graduação da Síndrome das Pernas Inquietas (EGSPI) para avaliar a gravidade dos sintomas da SPI. OBJETIVO: Traduzir, adaptar culturalmente e validar a EGSPI para o português do Brasil. MÉTODO: A escala foi vertida para o português, analisada, vertida novamente para o inglês e comparada com a versão original. Foi aplicada em 10 pacientes para adequação cultural. A linguagem foi ajustada e a versão final foi aplicada em 30 pacientes (13 homens, idade média de 58,88±14,82). RESULTADOS: Houve correlação da aplicação da escala entre três avaliadores. Foram necessárias adaptações lingüísticas para adequação cultural e o alfa de Chronbach mostrou confiabilidade de 80%. CONCLUSÃO: A EGSPI foi traduzida, adequada e validada para o português do Brasil, com boa validade e confiabilidade.Federal University of São Paulo Department of NeurologyFederal University of São Paulo Department of MedicineFederal University of São Paulo Hospital São Paulo Sleep LaboratoryUNIFESP, Department of NeurologyUNIFESP, Department of MedicineUNIFESP, Hospital São Paulo Sleep LaboratorySciEL

Anti-Tumor Effect against Human Cancer Xenografts by a Fully Human Monoclonal Antibody to a Variant 8-Epitope of CD44R1 Expressed on Cancer Stem Cells

BACKGROUND: CD44 is a major cellular receptor for hyaluronic acids. The stem structure of CD44 encoded by ten normal exons can be enlarged by ten variant exons (v1-v10) by alternative splicing. We have succeeded in preparing MV5 fully human IgM and its class-switched GV5 IgG monoclonal antibody (mAb) recognizing the extracellular domain of a CD44R1 isoform that contains the inserted region coded by variant (v8, v9 and v10) exons and is expressed on the surface of various human epithelial cancer cells. METHODS AND PRINCIPAL FINDINGS: We demonstrated the growth inhibition of human cancer xenografts by a GV5 IgG mAb reshaped from an MV5 IgM. The epitope recognized by MV5 and GV5 was identified to a v8-coding region by the analysis of mAb binding to various recombinant CD44 proteins by enzyme-linked immunosorbent assay. GV5 showed preferential reactivity against various malignant human cells versus normal human cells assessed by flow cytometry and immunohistological analysis. When ME180 human uterine cervix carcinoma cells were subcutaneously inoculated to athymic mice with GV5, significant inhibition of tumor formation was observed. Furthermore, intraperitoneal injections of GV5markedly inhibited the growth of visible established tumors from HSC-3 human larynx carcinoma cells that had been subcutaneously transplanted one week before the first treatment with GV5. From in vitro experiments, antibody-dependent cellular cytotoxicity and internalization of CD44R1 seemed to be possible mechanisms for in vivo anti-tumor activity by GV5. CONCLUSIONS: CD44R1 is an excellent molecular target for mAb therapy of cancer, possibly superior to molecules targeted by existing therapeutic mAb, such as Trastuzumab and Cetuximab recognizing human epidermal growth factor receptor family

Chemoenzymatic Synthesis of Homogeneous Ultralow Molecular Weight Heparins

Ultralow molecular weight (ULMW) heparins are sulfated glycans that are clinically used to treat thrombotic disorders. ULMW heparins range from 1500 to 3000 daltons, corresponding from 5 to 10 saccharide units. The commercial drug Arixtra (fondaparinux sodium) is a structurally homogeneous ULMW heparin pentasaccharide that is synthesized through a lengthy chemical process. Here, we report 10- and 12-step chemoenzymatic syntheses of two structurally homogeneous ULMW heparins (MW = 1778.5 and 1816.5) in 45 and 37% overall yield, respectively, starting from a simple disaccharide. These ULMW heparins display excellent in vitro anticoagulant activity and comparable pharmacokinetic properties to Arixtra, as demonstrated in a rabbit model. The chemoenzymatic approach is scalable and shows promise for a more efficient route to synthesize this important class of medicinal agent

An interaction between Nrf2 polymorphisms and smoking status affects annual decline in FEV1: a longitudinal retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>An Nrf2-dependent response is a central protective mechanism against oxidative stress. We propose that particular genetic variants of the <it>Nrf2 </it>gene may be associated with a rapid forced expiratory volume in one second (FEV₁) decline induced by cigarette smoking.</p> <p>Methods</p> <p>We conducted a retrospective cohort study of 915 Japanese from a general population. Values of annual decline in FEV₁were computed for each individual using a linear mixed-effect model. Multiple clinical characteristics were assessed to identify associations with annual FEV₁decline. Tag single-nucleotide polymorphisms (SNPs) in the <it>Nrf2 </it>gene (rs2001350, rs6726395, rs1962142, rs2364722) and one functional SNP (rs6721961) in the <it>Nrf2 </it>promoter region were genotyped to assess interactions between the <it>Nrf2 </it>polymorphisms and smoking status on annual FEV₁decline.</p> <p>Results</p> <p>Annual FEV₁decline was associated with smoking behavior and inversely correlated with FEV₁/FVC and FEV₁% predicted. The mean annual FEV₁declines in individuals with rs6726395 G/G, G/A, or A/A were 26.2, 22.3, and 20.8 mL/year, respectively, and differences in these means were statistically significant (p_corr= 0.016). We also found a significant interaction between rs6726395 genotype and smoking status on the FEV₁decline (p for interaction = 0.011). The haplotype rs2001350T/rs6726395A/rs1962142A/rs2364722A/rs6721961T was associated with lower annual decline in FEV₁(p = 0.004).</p> <p>Conclusions</p> <p>This study indicated that an Nrf2-dependent response to exogenous stimuli may affect annual FEV₁decline in the general population. It appears that the genetic influence of <it>Nrf2 </it>is modified by smoking status, suggesting the presence of a gene-environment interaction in accelerated decline in FEV₁.</p

Feeding Cues and Injected Nutrients Induce Acute Expression of Multiple Clock Genes in the Mouse Liver

The circadian clock is closely associated with energy metabolism. The liver clock can rapidly adapt to a new feeding cycle within a few days, whereas the lung clock is gradually entrained over one week. However, the mechanism underlying tissue-specific clock resetting is not fully understood. To characterize the rapid response to feeding cues in the liver clock, we examined the effects of a single time-delayed feeding on circadian rhythms in the liver and lungs of Per2::Luc reporter knockin mice. After adapting to a night-time restricted feeding schedule, the mice were fed according to a 4, 8, or 13 h delayed schedule on the last day. The phase of the liver clock was delayed in all groups with delayed feeding, whereas the lung clock remained unaffected. We then examined the acute response of clock and metabolism-related genes in the liver using focused DNA-microarrays. Clock mutant mice were bred under constant light to attenuate the endogenous circadian rhythm, and gene expression profiles were determined during 24 h of fasting followed by 8 h of feeding. Per2 and Dec1 were significantly increased within 1 h of feeding. Real-time RT-PCR analysis revealed a similarly acute response in hepatic clock gene expression caused by feeding wild type mice after an overnight fast. In addition to Per2 and Dec1, the expression of Per1 increased, and that of Rev-erbα decreased in the liver within 1 h of feeding after fasting, whereas none of these clock genes were affected in the lung. Moreover, an intraperitoneal injection of glucose combined with amino acids, but not either alone, reproduced a similar hepatic response. Our findings show that multiple clock genes respond to nutritional cues within 1 h in the liver but not in the lung

Peroxisome proliferator-activated receptor α (PPARα) mRNA expression in human hepatocellular carcinoma tissue and non-cancerous liver tissue

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptor α (PPARα) regulates lipid metabolism in the liver. It is unclear, however, how this receptor changes in liver cancer tissue. On the other hand, mouse carcinogenicity studies showed that PPARα is necessary for the development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer have been the focus of considerable attention. There have been no reports, however, demonstrating that PPARα is involved in the development of human liver cancer.</p> <p>Methods</p> <p>The subjects were 10 patients who underwent hepatectomy for hepatocellular carcinoma. We assessed the expression of PPARα mRNA in human hepatocellular carcinoma tissue and non-cancerous tissue, as well as the expression of target genes of PPARα, carnitine palmitoyltransferase 1A and cyclin D1 mRNAs. We also evaluated glyceraldehyde 3-phosphate dehydrogenase, a key enzyme in the glycolytic system.</p> <p>Results</p> <p>The amounts of PPARα, carnitine palmitoyltransferase 1A and glyceraldehyde 3-phosphate dehydrogenase mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of cyclin D1 mRNA tends to be higher in cancerous than non-cancerous sections. Although there was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections.</p> <p>Conclusion</p> <p>The present investigation indicated increased expression of PPARα mRNA and mRNAs for PPARα target genes in human hepatocellular carcinoma. These results might be associated with its carcinogenesis and characteristic features of energy production.</p

Various Spatiotemporal Expression Profiles of Anther-Expressed Genes in Rice

The male gametophyte and tapetum play different roles during anther development although they are differentiated from the same cell lineage, the L2 layer. Until now, it has not been possible to delineate their transcriptomes due to technical difficulties in separating the two cell types. In the present study, we characterized the separated transcriptomes of the rice microspore/pollen and tapetum using laser microdissection (LM)-mediated microarray. Spatiotemporal expression patterns of 28,141 anther-expressed genes were classified into 20 clusters, which contained 3,468 (12.3%) anther-enriched genes. In some clusters, synchronous gene expression in the microspore and tapetum at the same developmental stage was observed as a novel characteristic of the anther transcriptome. Noteworthy expression patterns are discussed in connection with gene ontology (GO) categories and gene annotations, which are related to important biological events in anther development, such as pollen maturation, pollen germination, pollen tube elongation and pollen wall formation