Leucemia linfocítica crônica: anormalidades cromossômicas e a sua relação com o estágio clínico CD38 e o ZAP-70

Chronic lymphocytic leukemia is the most prevalent type of leukemia in the West. It is characterized by an extremely variable clinical course. The aim of the study was to detect the most frequent chromosomal abnormalities in patients with CLL using FISH, and assess them regarding age, gender, clinical stage and CD38 and ZAP-70 expressions. We found 51.7% of the patients with chromosome abnormalities. The most frequent one was del 13q14 in 34.5% of cases. It was associated to other alterations in 17.2%. 17p13 deletions were found in 17.2% and trisomy 12 in 13.8% (in isolation in 6.9% and associated to del 13q14, in 6.9% of the cases). An 11q22 deletion was found in one case associated to a 13q14 deletion. To better evaluate the relationship between chromosome aberrations and other prognostic factors in CLL, two cytogenetics groups were considered: favorable (13q deletion in isolation and no alteration) and unfavorable outcomes (trisomy 12, 17p13 deletion, 11q22 deletion and two simultaneous alterations).The unfavorable alterations were more frequently seen among young individuals (<60y). There were more females (70%) than males in this group (p=0.04). In relation to the Binet's staging system, patients with unfavorable cytogenetic alterations, tended to be B and C stages, while in the favorable group prevailed patients in stage A. Additionally, patients with poor prognostic cytogenetics tended to express CD38 and ZAP-70 proteins.A leucemia linfocítica crônica (LLC) é o tipo de leucemia mais prevalente no Ocidente e é caracterizada por curso clínico extremamente variável. O objetivo deste estudo foi detectar as anomalias cromossômicas mais freqüentes em pacientes com LLC, empregando a técnica FISH, e correlacioná-las com idade, sexo, estádio clínico, expressão de CD 38 e ZAP-70. Foram encontradas alterações cromossômicas em 51,7% dos pacientes. A mais freqüente foi a del 13q14, observada em 34,5% dos casos e que esteve associada a outras anomalias em 17,2%. Deleção 17p13 foi encontrada em 17,2% e trissomia 12 em 13,8% (isolada em 6,9% e associada à del 13q14 em 6,9%). Deleção 11q22 foi observada em um caso em concomitância à del 13q14. Para melhor avaliar a relação entre alteração cromossômica e outros fatores prognósticos em LLC, dois grupos citogenéticos foram considerados: favorável (deleção 13q isolada e ausência de alterações) e desfavorável (trissomia 12, deleção 17p13, deleção 11q22 e duas anomalias simultâneas). As alterações desfavoráveis foram mais freqüentemente observadas em indivíduos jovens (<60 anos) e em mulheres (70%)(p=0,04). Em relação ao sistema de estadiamento de Binet, houve tendência dos pacientes com alterações cromossômicas desfavoráveis apresenteram-se nos estágios B e C enquanto no grupo favorável prevaleceram aqueles com estágio A. Em adição, pacientes com achados citogenéticos de prognóstico desfavorável tiveram tendência a expressar proteínas CD 38 e ZAP-70.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Effect of yogurt containing polydextrose, Lactobacillus acidophilus NCFM and Bifidobacterium lactis HN019: a randomized, double-blind, controlled study in chronic constipation

BACKGROUND: Constipation is a frequent complaint and the combination of a prebiotic and probiotics could have a potentially synergic effect on the intestinal transit. The present study therefore aims to investigate the combination of polydextrose (Litesse®), L. acidophilus NCFM® and B. lactis HN019 in a yogurt on intestinal transit in subjects who suffer from constipation. METHODS: Patients with constipation were randomly divided into two groups, Control Group (CG) and Treatment Group (TG), and had to eat 180 ml of unflavored yogurt every morning for 14 days. Those in the CG received only yogurt, while the TG received yogurt containing polydextrose, L. acidophilus NCFM® (ATCC 700396) and B. lactis HN019 (AGAL NM97/09513). RESULTS: Favourable clinical response was assessed since Agachan score had a significant reduction at the end of the study in both groups and tended to be better in the TG. The subjects in the treatment group also had a shorter transit time at the end of the intervention compared to the control group (p = 0.01). CONCLUSION: The product containing yogurt with polydextrose, B. lactis HN019 and L. acidophilus NCFM® significantly shortened colonic transit time after two weeks in the TG compared to CG and may be an option for treatment of constipation

Reactivity of paraquat with sodium salicylate: formation of stable complexes

Sodium salicylate (NaSAL) has been shown to be a promising antidote for the treatment of paraquat (PQ) poisonings. The modulation of the pro-oxidant and pro-inflammatory pathways, as well as the antithrombogenic properties of NaSAL are probably essential features for the healing effects provided by this drug. Nevertheless, a possible direct chemical reactivity between PQ and NaSAL is also a putative pathway to be considered, this hypothesis being the ground of the present study. In accordance, it is shown, for the first time that PQ and NaSAL react immediately in aqueous medium and within 2–3 min in the solid state. Photographs and scanning electron photomicrographs indicated that a new chemical entity is formed when both compounds are mixed. This assumption was corroborated by the evaluation of the melting point, and through several analytical techniques, namely ultraviolet/visible spectroscopy, nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS), liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry (LC/ESI/MS/MS) and infrared spectroscopy, which revealed that stable charge-transfer complexes are formed when PQ is mixed with NaSAL. LC/ESI/MS/MS allowed obtaining the stoichiometry of the charge-transfer complexes. In order to increase resolution, single value decomposition, acting as a filter, showed that the chargetransfer complexes withm/z 483, 643 and 803 correspond to the pseudo-molecular ions, respectively 1:2, 1:3 and 1:4 (PQ:NaSAL). In conclusion, these results provided a new and important mechanism of action of NaSAL against the toxicity mediated by PQ

Toll-like Receptor 4, F4/80 And Pro-inflammatory Cytokines In Intestinal And Mesenteric Fat Tissue Of Crohn's Disease.

Crohn's disease (CD) is a chronic intestinal ailment with a multifactorial etiology, whose incidence has increased during the last three decades. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected nearby the affected intestinal area; however, there are few studies on this aspect. To evaluate inflammatory activity in intestinal mucosa and mesenteric fat tissue of patients with CD and controls. Ten patients with ileocecal CD and 16 patients with non-inflammatory disease (control groups) were studied. The specimens were snap-frozen and the expression of TLR-4, F4/80, IL1-β and IL-6 were determined by immunoblot of protein extracts. TLR4 RNA level were measured using RT-PCR. The t Test was applied (p<0.05). The local ethical committee approved the study. The intestinal mucosa of CD group had significantly higher protein levels of TLR-4, F4/80, IL-1β and IL-6 than the controls. The gene expression of TLR4 was lower in the intestinal mucosa of CD compared to the control group. Regard the mesenteric fat tissue, there was no statistical difference related to TLR-4, F4/80, IL-1β and IL-6 proteins expression. These findings may result from an up-regulation of macrophage activation and intracellular pathways activated by bacterial antigens, which are more important in intestinal mucosa than fat tissue in CD patients. This may represent an anomalous regulation of innate immunity and could contribute to the production of proinflammatory mediators and disease development.698-10

Abstracts

Tradução, para a língua inglesa, dos resumos dos artigos publicados nesta edição

Uso de árvores nativas em pastagens agroecológicas

O conhecimento tradicional tem sido a base da parceria entre o Centro de Tecnologias Alternativas, as organizações dos agricultores familiares da Zona da Mata de Minas Gerais e as Universidades Federais de Viçosa e, mais recentemente, de Lavras. O objetivo desse trabalho foi identificar o conhecimento tradicional sobre os usos comuns de árvores nativas em pastagens de famílias agricultoras dos municípios de Divino e Araponga, aplicando metodologias participativas (observação participante e entrevista semi-estruturada). O principal uso da terra na região é com café e pastagens. Foi observado pelas famílias que os animais comem ramos de Solanum mauritianum, Senna macranthera, Aegiphila sellowiana e Inga edulis. De acordo com as famílias, a maioria das árvores já estava na pastagem antes do capim. É necessário aprofundamento que dialogue com o aprendizado de famílias agricultoras.Traditional knowledge has been the main base of the partnership among the Center of Alternative Technologies, the organizations of family farmers of Zona da Mata of Minas Gerais and the Federal Universities of Viçosa and, more recently, of Lavras. The objective was to identify the traditional knowledge about the common uses of native trees in the pastures of the properties of family farmers in the municipalities of Divino and Araponga, applying qualitative methodologies (participant observation and semi-structured interviews). The land use in the region is mainly coffee and pastures. Was observed by the families that the animals feed themselves with branches of Solanum mauritianum, Senna macranthera, Aegiphila sellowiana and Inga edulis. According to the families the majority of the trees was already in the field before the grass. It is necessary to deep the dialogue to keep leaning and exchange knowledge with smallholders families.Eje A1 Sistemas de producción de base agroecológica (Trabajos científicos)Facultad de Ciencias Agrarias y Forestale

Immobilization and application of the recombinant xylanase GH10 of Malbranchea pulchella in the production of xylooligosaccharides from hydrothermal liquor of the eucalyptus (Eucalyptus grandis) wood chips

Xylooligosaccharides (XOS) are widely used in the food industry as prebiotic components. XOS with high purity are required for practical prebiotic function and other biological benefits, such as antioxidant and inflammatory properties. In this work, we immobilized the recombinant endo-1,4-β-xylanase of Malbranchea pulchella (MpXyn10) in various chemical supports and evaluated its potential to produce xylooligosaccharides (XOS) from hydrothermal liquor of eucalyptus wood chips. Values >90% of immobilization yields were achieved from amino-activated supports for 120 min. The highest recovery values were found on Purolite (142%) and MANAE-MpXyn10 (137%) derivatives, which maintained more than 90% residual activity for 24 h at 70 °C, while the free-MpXyn10 maintained only 11%. In addition, active MpXyn10 derivatives were stable in the range of pH 4.0–6.0 and the presence of the furfural and HMF compounds. MpXyn10 derivatives were tested to produce XOS from xylan of various sources. Maximum values were observed for birchwood xylan at 8.6 mg mL−1 and wheat arabinoxylan at 8.9 mg mL−1, using Purolite-MpXyn10. Its derivative was also successfully applied in the hydrolysis of soluble xylan present in hydrothermal liquor, with 0.9 mg mL−1 of XOS after 3 h at 50 °C. This derivative maintained more than 80% XOS yield after six cycles of the assay. The results obtained provide a basis for the application of immobilized MpXyn10 to produce XOS with high purity and other high-value-added products in the lignocellulosic biorefinery field.The authors gratefully acknowledge FAPESP (São Paulo Research Foundation, grants No: 2018/07522-6) and FCT (POCI-01-0145-FEDER-032206)—transnational cooperation project EcoTech, and National Institute of Science and Technology of Bioethanol, INCT, CNPq 465319/2014-9/FAPESP n ◦ 2014/50884- 5) for financial support. Research scholarships were granted to RCA, DA, and JCSS by FAPESP (Grant No: 2020/00081-4, 2020/15510-8, and 2019/21989-7, respectively), to CCVD and VEP by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Finance Code 001).info:eu-repo/semantics/publishedVersio

Interaction of leptospira elongation factor tu with plasminogen and complement factor h: a metabolic leptospiral protein with moonlighting activities

The elongation factor Tu (EF-Tu), an abundant bacterial protein involved in protein synthesis, has been shown to display moonlighting activities. Known to perform more than one function at different times or in different places, it is found in several subcellular locations in a single organism, and may serve as a virulence factor in a range of important human pathogens. Here we demonstrate that Leptospira EF-Tu is surface-exposed and performs additional roles as a cell-surface receptor for host plasma proteins. It binds plasminogen in a dose-dependent manner, and lysine residues are critical for this interaction. Bound plasminogen is converted to active plasmin, which, in turn, is able to cleave the natural substrates C3b and fibrinogen. Leptospira EF-Tu also acquires the complement regulator Factor H (FH). FH bound to immobilized EF-Tu displays cofactor activity, mediating C3b degradation by Factor I (FI). In this manner, EF-Tu may contribute to leptospiral tissue invasion and complement inactivation. To our knowledge, this is the first description of a leptospiral protein exhibiting moonlighting activitiesFAPESP, 00/11624-