The role of bendamustine in the treatment of indolent non-Hodgkin lymphoma

There is no consensus on recommendations for the treatment of relapsed and refractory indolent non-Hodgkin lymphoma (NHL). Bendamustine hydrochloride (bendamustine) has recently been approved for treatment of these patients. Bendamustine is a uniquely structured alkylating agent that lacks cross-resistance with other alkylators. This agent has a high degree of activity against a variety of tumor cell lines. Clinically, bendamustine has demonstrated activity against indolent NHL, chronic lymphocytic lymphoma, multiple myeloma and mantle cell lymphoma. Moreover, studies have validated its activity in patients with indolent NHL who are resistant to purine analogs and rituximab. The cytotoxic activity of bendamustine has been shown to be synergistic with rituximab in hematological malignancies. The incidence of alopecia is significantly less than with other alkylating agents. Myelosuppression is the major toxicity associated with bendamustine

Graphene oxide toxicological effects on daphnia and hydra.

The increased use of nanomaterials products requires robust strategies to identify risks when they are released into the environment. Graphene and its derivatives are promising candidates for biomedical applications and as potential advanced water purification agents. However, little is known about their ecotoxicological risks. Aquatic toxicity tests are performed with different aquatic organisms as daphnia and hydra in order to evaluate the risks resulting from the presence of graphene oxide (GO) in the environment. The following GO concentrations were tested: 0, 1, 10 and 100 mg.L-1. Acute toxicity to D. magna was evaluated in a period of 48 hours when was recorded the number of moving subjects in order to determine the CE5024h and CE5048h (n = 24 / group). The percentage of daphnia presenting mobility after 48 hours of exposure was greater than 60% in all groups. There was a concentration effect of graphene oxide (p = 0.02) and mobility was 20% lower in group exposed to 100 mg.L-1 than the control group. To evaluate the occurrence of the effect of sublethal concentrations for 96 h, it was evaluate neonate D. similis growth rate through exposure to the same conditions used for acute toxicity testing (n = 10 / group). The bodies were photographed at the start of the test and every 24 hours. Also, there was studied the effect of the organisms mobility during 96 hours calculating the median survival time of the population, defined as the average time between the start of exposure and the immobility of organisms. There was a sharp decline when the organisms were subjected to 100 mg. L-1 GO. The Hydra attenuata test was performed for 96h. The organisms were observed every 24 hours for the presence of changes ranging from tentacles with bulbs (low toxicity) till shortening of the tentacles (severe toxicity), tulip aspect and disintegration (lethal). A mean score for each concentration was calculated. No mortality was observed in any concentration tested. However, it was observed some morphological alterations after 72h of 100.0 mg.L-1 exposure as clubbed and shortened tentacles and body slightly contracted. Exposures of the test organisms indicate that GO do not present a lethal risk or adversely affect them at concentrations lower to 10.0 mg. L-1. Even though the results apparently demonstrate that GO currently do not pose a serious risk, it may exert some damage in aquatic organisms tested at higher doses

Systematic Analytical Approach to Correlation Functions of Resonances in Quantum Chaotic Scattering

We solve the problem of resonance statistics in systems with broken time-reversal invariance by deriving the joint probability density of all resonances in the framework of a random matrix approach and calculating explicitly all n-point correlation functions in the complex plane. As a by-product, we establish the Ginibre-like statistics of resonances for many open channels. Our method is a combination of Itzykson-Zuber integration and a variant of nonlinear $\sigma-$model and can be applied when the use of orthogonal polynomials is problematic.Comment: 4 pages, no figures. Misprints corrected, some details on single-channel and many-channel cases are adde

Effects of graphene oxide on aquatic macrophyte under the influence of humic substances.

The behavior of nanostructured graphene oxide (GO) in the environment is complex and must be completely understood to evaluate the risk involved. Studies show that humic acid (HA) can stabilize nanomaterials in water and change its behavior. The aquatic macrophyte duckweed (Lemna minor) is a good plant model for adverse effects evaluation of many test-materials due to its fast growth and small size. This study assessed the effect of GO, with and without HA, on the growth of L. minor on fronds number and biomass changes. The plants were exposed during 7 days to the nominal concentrations of GO equals to 0.0 (control), 0.1, 1.0, 10.0 and 100.0 mg L-1, in the absence or in the presence of 20 mg L-1 of HA. Tests were conducted in multiwell polystyreneplates where each well contained two fronds at the start of the experiment. The number of replicates for each test?concentration was 24 wells. The plants were exposed to a constant photoperiod (24:0, light:dark cycle) supplied by white fluorescent lamps (~700 lux) at the temperature of 20± 2 ºC. The fronds number was counted daily and the wet weight was assessed at the end of the experiment. The concentration that promoted 50% of inhibition in the growth rate in terms of fronds number (EC50-7d growth) and the concentration that promoted 50% of wet weight reduction (EC50-7d biomass) were calculated. The reduction of the growth rate by GO at the concentration of 100 mg L-1 was remarkable detected (P 100 mg L-1. This value attributes a practically non-toxicity for the test-material in terms of fronds production. On the other hand, the calculated EC50-7d biomass for the GO in the presence of HA or not was 2.8 and 2.4 mg L-1 respectively. These results indicate that the adverse effects of GO in L. minor are more pronounced on the biomass production since it was clearly observed that reductions in the fronds sizes were greater than in the fronds number. The EC50-7d biomass values assigns a moderate toxicity of GO to L. minor and these data may be useful for the establishment of maximum concentrations limits of this material in water bodies

Statistics of S-matrix poles for chaotic systems with broken time reversal invariance: a conjecture

In the framework of a random matrix description of chaotic quantum scattering the positions of $S-$matrix poles are given by complex eigenvalues $Z_i$ of an effective non-Hermitian random-matrix Hamiltonian. We put forward a conjecture on statistics of $Z_i$ for systems with broken time-reversal invariance and verify that it allows to reproduce statistical characteristics of Wigner time delays known from independent calculations. We analyze the ensuing two-point statistical measures as e.g. spectral form factor and the number variance. In addition we find the density of complex eigenvalues of real asymmetric matrices generalizing the recent result by Efetov\cite{Efnh}.Comment: 4 page

Semiclassical analysis of the quantum interference corrections to the conductance of mesoscopic systems

The Kubo formula for the conductance of a mesoscopic system is analyzed semiclassically, yielding simple expressions for both weak localization and universal conductance fluctuations. In contrast to earlier work which dealt with times shorter than $O(\log \hbar^{-1})$, here longer times are taken to give the dominant contributions. For such long times, many distinct classical orbits may obey essentially the same initial and final conditions on positions and momenta, and the interference between pairs of such orbits is analyzed. Application to a chain of $k$ classically ergodic scatterers connected in series gives the following results: $-{1 \over 3} [ 1 - (k+1)^{-2} ]$ for the weak localization correction to the zero--temperature dimensionless conductance, and ${2 \over 15} [ 1 - (k+1)^{-4} ]$ for the variance of its fluctuations. These results interpolate between the well known ones of random scattering matrices for $k=1$, and those of the one--dimensional diffusive wire for $k \rightarrow \infty$.Comment: 53 pages, using RevTeX, plus 3 postscript figures mailed separately. A short version of this work is available as cond-mat/950207

Significant increase in azithromycin "resistance" and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019

Background: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2019 (26 countries), linked to patient epidemiological data, and compared with data from previous years. Methods: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST clinical breakpoints, where available) of 3239 N. gonorrhoeae isolates from 26 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-test and the Pearson's χ2 test was used to assess significance of odds ratios for associations between patient epidemiological data and antimicrobial resistance. Results: European N. gonorrhoeae isolates collected between 2016 and 2019 displayed shifting MIC distributions for; ceftriaxone, with highly susceptible isolates increasing over time and occasional resistant isolates each year; cefixime, with highly-susceptible isolates becoming increasingly common; azithromycin, with a shift away from lower MICs towards higher MICs above the EUCAST epidemiological cut-off (ECOFF); and ciprofloxacin which is displaying a similar shift in MICs as observed for azithromycin. In 2019, two isolates displayed ceftriaxone resistance, but both isolates had MICs below the azithromycin ECOFF. Cefixime resistance (0.8%) was associated with patient sex, with resistance higher in females compared with male heterosexuals and men-who-have-sex-with-men (MSM). The number of countries reporting isolates with azithromycin MICs above the ECOFF increased from 76.9% (20/26) in 2016 to 92.3% (24/26) in 2019. Isolates with azithromycin MICs above the ECOFF (9.0%) were associated with pharyngeal infection sites. Following multivariable analysis, ciprofloxacin resistance remained associated with isolates from MSM and heterosexual males compared with females, the absence of a concurrent chlamydial infection, pharyngeal infection sites and patients ≥ 25 years of age. Conclusions: Resistance to ceftriaxone and cefixime remained uncommon in EU/EEA countries in 2019 with a significant decrease in cefixime resistance observed between 2016 and 2019. The significant increase in azithromycin "resistance" (azithromycin MICs above the ECOFF) threatens the effectiveness of the dual therapy (ceftriaxone + azithromycin), i.e., for ceftriaxone-resistant cases, currently recommended in many countries internationally and requires close monitoring.The study was funded by the European Centre for Disease Prevention and Control (Framework Contract No. ECDC/2017/004). The funding body designed, initiated and coordinated the study as well as assisted in the interpretation of the data, development and final approval of the manuscriptS

Efeitos da exposição aguda ao dimetoato em microcrustáceos e anelídeos.

Resumo: O dimetoato é um inseticida organofosforado de amplo espectro que penetra no corpo através da ingestão, inalação e contato com a pele. Em animais, pode ser metabolizado em produtos de oxidação mais tóxicos afetando muitos organismos não-alvo, incluindo invertebrados aquáticos e do solo. Tanto o microcrustáceo Daphnia magna quanto a minhoca Eisenia fetida são organismos adequados para ensaios de toxicidade, uma vez que pode ser facilmente criados e possuem curto ciclo de vida. O objetivo desse estudo foi avaliar a toxicidade aguda (48h) do dimetoato no microcrustáceo Daphnia magna enquanto organismo-teste aquático e avaliar os efeitos do dimetoato grau técnico sobre a sobrevivência de Eisenia fetida. Procurou-se também verificar a viabilidade do método de contato com papel de filtro para avaliação de ensaios de toxicidade aguda com minhocas. A CE50 para Daphnia magna foi de 0,99 mg/L com intervalo de confiança 95% de 1,22 - 1,54. A CL50 foi de 1083,55 mg/L de dimetoato grau técnico com limites inferiores e superiores a 95% de 711,23 ? 1375,55 mg/L para a E. fetida. O dimetoato grau técnico apenas apresentou letalidade a 50% da população em concentração acima de 1000 mg/L o que pode ser considerado praticamente não tóxico a organismos não-alvo do solo. Foi evidenciada também a eficiência do método de contato com papel de filtro como ferramenta para avaliação de toxicidade para E. fetida.bitstream/item/138620/1/2015AA061.pd