High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance

It has been postulated that monitoring measurable residual disease (MRD) could be used as a surrogate marker of progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients after treatment with immunochemotherapy regimens. In this study, we analyzed the outcome of 84 patients at 3 years of follow-up after first-line treatment with fludarabine, cyclophosphamide and rituximab (FCR) induction followed by 36 months of rituximab maintenance thearpy. MRD was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10-4. Eighty out of 84 evaluable patients (95.2%) achieved at least a partial response or better at the end of induction. After clinical evaluation, 74 patients went into rituximab maintenance and the primary endpoint was assessed in the final analysis at 3 years of follow-up. Bone marrow (BM) MRD analysis was performed after the last planned induction course and every 6 months in cases with detectable residual disease during the 36 months of maintenance therapy. Thirty-seven patients (44%) did not have detectable residual disease in the BM prior to maintenance therapy. Interestingly, 29 patients with detectable residual disease in the BM after induction no longer had detectable disease in the BM following maintenance therapy. After a median followup of 6.30 years, the median overall survival (OS) and PFS had not been reached in patients with either undetectable or detectable residual disease in the BM, who had achieved a complete response at the time of starting maintenance therapy. Interestingly, univariate analysis showed that after rituximab maintenance OS was not affected by IGHV status (mutated vs. unmutated OS: 85.7% alive at 7.2 years vs. 79.6% alive at 7.3 years, respectively). As per protocol, 15 patients (17.8%), who achieved a complete response and undetectable peripheral blood and BM residual disease after four courses of induction, were allowed to stop fludarabine and cyclophosphamide and complete two additional courses of rituximab and continue with maintenance therapy for 18 cycles. Surprisingly, the outcome in this population was similar to that observed in patients who received the full six cycles of the induction regimen. These data show that, compared to historic controls, patients treated with FCR followed by rituximab maintenance have high-quality responses with fewer relapses and improved OS. The tolerability of this regime is favorable. Furthermore, attaining an early undetectable residual disease status could shorten the duration of chemoimmunotherapy, reducing toxicities and preventing long-term side effects. The analysis of BM MRD after fludarabine-based induction could be a powerful predictor of post-maintenance outcomes in patients with CLL undergoing rituximab maintenance and could be a valuable tool to identify patients at high risk of relapse, influencing further treatment strategies

Experimental osteoarthritis in rabbits: lesion progression

The aim of this study was to evaluate the progression of lesions in different stages of osteoarthritis (OA) experimental by radiography (RX), computed tomography (CT), macroscopic and histopathology, linking these different diagnostic methods, helped to provide information that helps the best time for the therapeutic approach. Four experimental periods were delineated at 3, 6, 9 and 12 weeks after induction of OA, known as PI, PII, PIII and PIV, respectively, each with six animals. We evaluated the five compartments of the femorotibial joint: medial femoral condyle (MFC), lateral femoral condyle (LFC), medial tibial plateau (MTP), lateral tibial plateau (LTP) and femoral trochlea (FT). Therefore we established an index by compartment (IC) and by adding such an index was estimated joint femorotibial (IFT). It was observed that the CFM was the compartment with the highest IC also differed significantly (p<0.05) from other compartments. Compartments showed no significant difference (p&gt;0.05) between the PI and PII, however contrary fact occurred between the PII and PIII (p<0.05), PIII and PIV (p<0.01) and between PI and PIV (p<0.001). Similarly the IFT, showed a significant difference in the animals of PIV compared to PI (p<0.001), PII (p<0.001) and PIII (p<0.01), and there was no statistical difference (p&gt; 0.05) between the PI and PII. In the variation of the average interval between periods, there was a higher value between the PIII PIV and for the other intervals of time periods (PI, PII, and PIII-PII). However, these intervals showed no statistically significant difference (p&gt;0.05). Through the RX, CT, macroscopic and histopathological findings, we found similar patterns among individuals within the same period demonstrating a gradual progression of the disease. These results show that between 3 and 6 weeks progression of the lesion is slower and probably also can be reversed in comparison to other ranges where proved further progression between 9 and 12 weeks after induction of trauma OA. These results may provide a better therapeutic approach aimed at reversing the lesions in early stages of OA. We conclude that the interconnection of the four diagnostic methods individually classified into scores, which were unified in both indices in the evaluation by the femorotibial joint compartment and may represent a diagnostic condition closer to the true condition of the injury and its progression

Formas orgânicas e inorgânicas de mobilização do cálcio no solo

A falta de Ca e a presença de Al na subsuperfície do solo restringem o crescimento das raízes. A eficiência da calagem aplicada na superfície do solo na neutralização da acidez subsuperficial é limitada. Foram conduzidos experimentos de laboratório com colunas de PVC para avaliar técnicas orgânicas e inorgânicas na mobilidade do Ca em solo com carga variável. Foram conduzidos dois experimentos com sais de Ca: CaCO3, CaSO4, Ca(NO3)2, Ca-acetato e Ca-citrato, e outro com CaCO3 associado com resíduos de aveia preta, trigo e leucena. Avaliaram-se os teores de Ca trocável em solucão de KCl 1M nas profundidades de 0 a 5, 5 a 10, 10 a 20, 20 a 30, 30 a 40 e 40 a 50cm. A eficiência dos sais na mobilidade de Ca seguiu a ordem: NO3 > Acetado > Citrato > SO4 > CO3. Os resíduos de plantas forma eficientes na mobilização do Ca na seguinte ordem: aveia > leucena > trigo. Atribuiu-se à formação de complexos organo-metálico a responsabilidade pela mobilização do Ca no solo associada com a calagem e os resíduos vegetais.<br>Lack of Ca and often the presence of Al in subsoil restrict crop-root proliferation. The efficacy of soil surface liming in neutralize subsoil acidity is limited. Laboratory experiments were conducted with leaching columns to evaluate some organic and inorganic techniques to accelerate the mobility of Ca in a variable charge soil. Two different experiments were conducted, one with Ca-salts: CaCO3, CaSO4, Ca(NO3)2, Ca-acetate, and Ca-citrate; and another one with CaCO3 plus plant residues: black oat (Avena strigosa), wheat (Triticum aestivum) and leucaena (Leucaena leucocephala). The observations included MKCl exchangeable Ca in 0 to 5, 5 to 10, 10 to 20, 20 to 30, 30 to 40 and 40 to 50 cm soil depth. The effects of CaCO3 without plant residue was limited to the upper 10 cm of the profile. The efficacy of Ca-salts on the mobility of Ca ex followed the order: NO3 > Acetate > Citrate > SO4 > CO3. Plant residues were highly efficient as Ca-carrier in the following order black oat > leucaena > wheat. Metal-organic complexes were assumed to be responsible for the movement of Ca in the profile associated with lime and plant residues

VIGOR DE SEMENTES DE MILHO (Zea mays L.) AVALIADO PELA PRECOCIDADE DE EMISSÃO DA RAIZ PRIMÁRIA EVALUATION OF CORN (Zea mays L.) SEED VIGOR THROUGH THE PRECOCITY OF PRIMARY ROOT EMISSION

Foi desenvolvido trabalho baseado na determinação da precocidade da emissão da raiz primária de sementes de milho, em dez lotes de um mesmo cultivar. Este processo constou da distribuição de 200 sementes de cada lote sobre folhas de papel umedecido e, também, rolos de papel, que permaneceram em germinador a 25 °C; de 12 em 12 horas, aquelas que apresentaram emissão da raiz primária foram removidas, contadas e anotadas. Para estabelecer comparação entre os métodos e os lotes, paralelamente, as sementes eram avaliadas através da determinação do grau de umidade, dos testes de germinação e de vigor (primeira contagem, teste de frio com solo e emergência de plântulas em campo). Concluiu-se que há possibilidade de se utilizar o teste de emissão da raiz primária, em rolos de papel, para a avaliação do vigor de sementes de milho.<br>The objectives of this study were to evaluate the variability of the emission of seed radicle of corn (Zea mays L.) and to establish indexes of primary root emission to test the vigor of commercial seed lots. Samples of corn seeds not treated with fungicides, were taken from ten lots of the same cultivar. Two hundred seeds from each lot were distributed on wetted paper towels and also within paper rolles at 25 °C. Each 12 hours, seeds with primary root emission were counted and removed. Indexes of primary root emission were calculated and compared to conventional laboratory tests (first count; accelerated aging; cold test) and field emergence. It was concluded that the primary root emission test, in rolled paper towels can be of great value for evaluating the vigor of corn seeds

Características e potencial tecnológico da carne da capivara Characteristcs and technological potential of the capybara meat

A carne de capivara tem conquistado espaço no mercado de carnes exóticas, justificando estudos que auxiliem no conhecimento de suas características e no aperfeiçoamento do seu processo de obtenção. Com esse objetivo, neste trabalho, os músculos Longissimus dorsi e Semimembranosus provenientes de animal macho, com idade entre 12 e 18 meses, foram submetidos a procedimentos analíticos visando a avaliar suas características e seu comportamento quanto aos aspectos tecnológicos. A carne apresentou um baixo teor de gordura, de 0,4% e 0,3% para os músculos L. dorsi e Semimembranosus, respectivamente. Foi observada uma correlação inversa (P<0,001) entre o comprimento do sarcômero e a força de cisalhamento. O comprimento de sarcômero do m. L. dorsi, em comparação com o m. Semimembranosus, foi menor (P<0,001: 1,88mim e 2,43mim, respectivamente), e a força de cisalhamento foi maior (P<0,001: 11,2kg e 9,1kg, respectivamente), indicando ser a carne do pernil mais macia que o lombo. Além disso, a partir de aparas e vísceras, foram elaborados produtos cárneos, de acordo com formulações-padrão para hambúrguer, patê e mortadela. Esses produtos foram submetidos à análise sensorial, obtendo uma boa aceitabilidade.<br>The good rank capybara meat has reached within the exotic meat market justifies studies on its physical-chemical composition and also on the improvement of the production process. With that aim, Longissimus dorsi and Semimembranosus muscles of male animals ageing 12 to 18 months were evaluated about composition and technological properties. It was found a low fat content in capybara meat - 0.4% and 0.3% for L. dorsi and Semimembranosus muscles, respectively. A inverse correlation (P<0.001) was found between sarcomere length and shear force. L. dorsi showed a shorter sarcomere lenght and a higher shear force (P<0.001) than Semimembranosus muscle (1.88 mum and 2.43 mum; 11.2 kg and 9.1kg, respectively), what denotes that capybara ham meat is tenderer than loin meat. Moreover, trimmings and viscera were used in the elaboration of meat products as hamburger, pátê and mortadella. Sensory analysis of those products showed good acceptance