O tratamento e a sobrevida no mieloma múltiplo

Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Departamento de Clinica Medica

Scaling laws for soliton pulse compression by cascaded quadratic nonlinearities

We present a detailed study of soliton compression of ultra-short pulses based on phase-mismatched second-harmonic generation (\textit{i.e.}, the cascaded quadratic nonlinearity) in bulk quadratic nonlinear media. The single-cycle propagation equations in the temporal domain including higher-order nonlinear terms are presented. The balance between the quadratic (SHG) and the cubic (Kerr) nonlinearity plays a crucial role: we define an effective soliton number -- related to the difference between the SHG and the Kerr soliton numbers -- and show that it has to be larger than unity for successful pulse compression to take place. This requires that the phase mismatch be below a critical level, which is high in a material where the quadratic nonlinearity dominates over the cubic Kerr nonlinearity. Through extensive numerical simulations we find dimensionless scaling laws, expressed through the effective soliton number, which control the behaviour of the compressed pulses. These laws hold in the stationary regime, in which group-velocity mismatch effects are small, and they are similar to the ones observed for fiber soliton compressors. The numerical simulations indicate that clean compressed pulses below two optical cycles can be achieved in a $\beta$-barium borate crystal at appropriate wavelengths, even for picosecond input pulses.Comment: 11 pages, 8 figures, resubmitted version, to appear in October issue of J. Opt. Soc. Am. B. Substantially revised, updated mode

Espresso coffees, caffeine and chlorogenic acid intake: potential health implications

HPLC analysis of 20 commercial espresso coffees revealed 6-fold differences in caffeine levels, a 17-fold range of caffeoylquinic acid contents, and 4-fold differences in the caffeoylquinic acid:caffeine ratio. These variations reflect differences in batch-to-batch bean composition, possible blending of arabica with robusta beans, as well as roasting and grinding procedures, but the predominant factor is likely to be the amount of beans used in the coffee-making/barista processes. The most caffeine in a single espresso was 322 mg and a further three contained >200 mg, exceeding the 200 mg day−1 upper limit recommended during pregnancy by the UK Food Standards Agency. This snap-shot of high-street expresso coffees suggests the published assumption that a cup of strong coffee contains 50 mg caffeine may be misleading. Consumers at risk of toxicity, including pregnant women, children and those with liver disease, may unknowingly ingest excessive caffeine from a single cup of espresso coffee. As many coffee houses prepare larger volume coffees, such as Latte and Cappuccino, by dilution of a single or double shot of expresso, further study on these products is warranted. New data are needed to provide informative labelling, with attention to bean variety, preparation, and barista methods

RNA interference against polo-like kinase-1 in advanced non-small cell lung cancers

Worldwide, approximately one and a half million new cases of lung cancer are diagnosed each year, and about 85% of lung cancer are non-small cell lung cancer (NSCLC). As the molecular pathogenesis underlying NSCLC is understood, new molecular targeting agents can be developed. However, current therapies are not sufficient to cure or manage the patients with distant metastasis, and novel strategies are necessary to be developed to cure the patients with advanced NSCLC

Sterilizing Activity of Second-Line Regimens Containing TMC207 in a Murine Model of Tuberculosis

RATIONALE: The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model. OBJECTIVE AND METHODS: Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model). MEASUREMENTS: Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU) counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment. MAIN RESULTS: The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin) was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide). When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide. CONCLUSIONS: In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18-24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside

同型な基本カンドルをもつリボン2 次元結び目とリボントーラス結び目の基本バイカンドル

広島大学(Hiroshima University)博士(理学)Sciencedoctora

<原著>培養軟骨細胞の分化機能発現と細胞増殖動態に関する実験的研究

The present study was undertaken to investigate the relationship among cell morphology, proliferation, and maturation of chondrocytes in primary cultures. Chondrocytes were isolated from the growth cartilages of the rat ribs and cultured for 6 days. In situ DNA cytofluorometry using an inverted epi-illumination cytofluorometer (Nikon P1-I) and 3H-thymidine autoradiography were carried out for the correlated analysis of cell morphology and proliferation. Cytoskeletal staining with fluorescent phalloidin and 35S-sulphate autoradiography were also performed. In addition, in situ hybridization to c-myc mRNA was carried out using DNA probe. According to the results obtained, the cultured chondrocytes were composed of mixed populations of large, polygonal cells and of small, round cells. The round cells showed a significantly higher 35S uptake than the polygonal cells. The cytoskeletal staining clearly revealed stress fibers in the cytoplasm of the polygonal cells, whereas only a fine filamentous structure was shown in the cytoplasm of the round cells. In situ DNA cytofluorometry clearly demonstrated that cell proliferative activity was high in the polygonal cells and low in the round cells. In addition, 3H-thymidine autoradiography with cumulative labeling method revealed that the polygonal cells were changing into the small, round cells. C myc mRNA signals were detected in the cytoplasm of over a half of the round cells, whereas no evidence of c-myc expression were found in the polygonal cells. From these results, it appears that as the shape of the cultured chondrocytes shifts from polygonal to round, the cell proliferative activity decreases in association with cell differentiation. It was also suggested that c-myc mRNA is amplified in the well differentiated round chondrocytes, and not in the proliferative polygonal cells.従来の培養軟骨細胞を用いた研究から, 軟骨細胞の形態と分化機能発現の聞には, 関連性のあることが示されている. 著者らは, 成長軟骨細胞の培養系において細胞形態, 機能が明らかに異なっている2種類の細胞が存在することを見いだした. 本研究では, この培養系を用い, 軟骨細胞の形態・細胞増殖動態・分化機能発現の3者の関連性を総合的に把握することを目的とした. このための方法論として, 細胞形態別増殖動態解析には, in situ DNA 顕微蛍光測光法と3_H-サイミジンオートラジオグラフィーを行い, 分化機能の検索には35_S オートラジオグラフィーを用いた. また, FITC-ファロイジン染色法により, 軟骨細胞の形態と細胞骨格の関係についても調べた. 更に, 本研究では, 悪性腫瘍以外に, 胎生期の細胞や分化途上の細胞にも出現し, 細胞の分化・増殖に深く関係があると考えられている c-myc 遺伝子の発現の有無を, in situ DNA- mRNA hybridization 法を用いて検索した. 実験には, ラット肋軟骨から分離・培養した成長軟骨細胞を用いた. 培養開始4 - 6日目頃の成長軟骨細胞は, 大型多角形の扁平な胞体を持ち, 大きな核を有する細胞(以下, 多角形細胞と略す)と, 比較的小型で類円形ないし球状の胞体と小さな核を有する細胞(以下, 円形細胞と略す)の2種類の細胞から構成されていた. in situ DNA 顕微蛍光測光法による細胞増殖動態解析の結果, 多角形細胞は, 活発な増殖性を示す2倍体細胞と少数の4倍体から構成されているのに対し, 円形細胞は, ほとんど増殖活性を持たない2倍体細胞から構成されていることが判った. 3_H-サイミジンの30分標識の結果から, 多角形細胞の標準率は11%, 円形細胞の標識率は0. 5%であり, その標識率の経時的変化はほとんど認められなかった. 3_H-サイミジンの持続標識実験の結果から, 多角形細胞が円形細胞に形態的に変化することが示唆された. また, 35_S オートラジオグラフィーより, 多角形細胞は, 軟骨基質の産生能が低く, 他方, 円形細胞では, 基質産生が亢進していることがわかった. FITC-ファロイジン染色によるアクチンの細胞内分布パタンを, 両細胞で比較したところ, 多角形細胞ではストレスファイバーがよく発達しているのに対し, 円形細胞には, 分断された線維性構造のみが観察された. 以上の結果をまとめると, 培養軟骨細胞の形態・増殖・分化の3者の間には, たがいに密接な関連が有り, 多角形細胞から円形細胞への形態変化に伴って, 増殖活性が低下し, 分化機能が発現されることが判明した. 次に, c-myc 遺伝子の発現の有無を in situ hybridization 法を用いて検索したところ, 円形細胞の過半数に, c-myc mRNA のシグナルが検出された. このことから, 軟骨細胞では, 分化機能発現と関連して c-myc 遺伝子が発現される可能性が示唆された