DNA damage and aberrant crypt foci as putative biomarkers to evaluate the chemopreventive effect of annatto (Bixa orellana L.) in rat colon carcinogenesis

Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of such potential chemopreventive agents. Colon cancer is one of the highest incidence rates throughout the world and some evidences have indicated carotenoids as possible agents that decrease the risk of colorectal cancer. In the present study, we evaluate the activity of annatto (Bixa orellaria L.), a natural food colorant rich in carotenoid, on the formation of aberrant crypt foci (ACF) induced by dimethy1hydrazine (DMH) in rat colon. Further, we investigate, the effect of annatto on DMH-induced DNA damage, by the comet assay. Male Wistar rats were given s.c. injections of DMH (40 mg/kg body wt.) twice a week for 2 weeks to induce ACE They also received experimental diets containing annatto at 20, 200 or 1000 ppm for five 5 weeks before (pre-treatment), or 10 weeks after (post-treatment) DMH treatment. In both protocols the rats were sacrificed on week 15th. For the comet assay, the animals were fed with the same experimental diets for 2 weeks. Four hours before the sacrifice, the animals received an s.c. injection of DMH (40 mg/kg body wt.). Under such conditions, dietary administration of 1000 ppm annatto neither induce DNA damage in blood and colon cells nor aberrant crypt foci in rat distal colon. Conversely, annatto was successful in inhibiting the number of crypts/colon (animal), but not in the incidence of DMH-induced ACF, mainly when administered after DMH. However, no antigenotoxic effect was observed in colon cells. These findings suggest possible chemopreventive effects of annatto through their modulation of the cryptal cell proliferation but not at the initiation stage of colon carcinogenesis. (c) 2005 Elsevier B.V. All rights reserved.

Two-Way Selection for Daily Gain and Feed Conversion in a Composite Rabbit Population

We conducted a two-way selection experiment in a composite rabbit population to investigate the responses to selection for postweaning ADG and feed conversion (FC). Two generations of crossing, followed by four generations of random pair matings, preceded three generations of selection. Selection was practiced within four lines: high-feed conversion (HFC), low-feed conversion (LFC), high gain (HG), and low gain (LG). Data on 1,446 rabbits from the random mating and selection generations were fitted to an animal model to estimate heritabilities of and the genetic correlation between ADG and FC. The two-trait model included rabbit and common litter random effects and line, generation, and sex fixed effects. Estimates of heritability of ADG and FC were .48 and .29, respectively, and the genetic correlation between them was -.82. Common litter environmental effects accounted for a proportion of .11 and . 13 of the phenotypic variation of the two traits, respectively. For ADG (in g/d) the regressions of mean breeding values on generation number during the selection period were 1.23 ± .12 (P < .01) in the HG line and -.86 ± .12 (P < .01) in the LG line; the regressions for FC (in g feed/g gain) were -.07 ± .01 (P < .01) in the HFC line and .03 ± .01 (P < .05) in the LFC line. Selection for ADG was effective in improving ADG and FC.

Biophysical Characterization of Interactions Involving Importin-α during Nuclear Import

Proteins containing the classical nuclear localization sequences (NLSs) are imported into the nucleus by the importin-α/β heterodimer. Importin-α contains the NLS binding site, whereas importin-β mediates the translocation through the nuclear pore. We characterized the interactions involving importin-α during nuclear import using a combination of biophysical techniques (biosensor, crystallography, sedimentation equilibrium, electrophoresis, and circular dichroism). Importin-α is shown to exist in a monomeric autoinhibited state (association with NLSs undetectable by biosensor). Association with importin-β (stoichiometry, 1:1; K D = 1.1 × 10 -8 M) increases the affinity for NLSs; the importin-α/β complex binds representative monopartite NLS (simian virus 40 large T-antigen) and bipartite NLS (nucleoplasmin) with affinities (K D = 3.5 × 10 -8 M and 4.8 × 10 -8 M, respectively) comparable with those of a truncated importin-α lacking the autoinhibitory domain (T-antigen NLS, K D = 1.7 × 10 -8 M; nucleoplasmin NLS, K D = 1.4 × 10 -8 M). The autoinhibitory domain (as a separate peptide) binds the truncated importin-α, and the crystal structure of the complex resembles the structure of full-length importin-α. Our results support the model of regulation of nuclear import mediated by the intrasteric autoregulatory sequence of importin-α and provide a quantitative description of the binding and regulatory steps during nuclear import.

Orphan nuclear receptor NGFI-B forms dimers with nonclassical interface

The orphan receptor nerve growth factor-induced B (NGFI-B) is a member of the nuclear receptor's subfamily 4A (Nr4a). NGFI-B was shown to be capable of binding both as a monomer to an extended half-site containing a single AAAGGTCA motif and also as a homodimer to a widely separated everted repeat, as opposed to a large number of nuclear receptors that recognize and bind specific DNA sequences predominantly as homo- and/or heterodimers. To unveil the structural organization of NGFI-B in solution, we determined the quaternary structure of the NGFI-B LBD by a combination of ab initio procedures from small-angle X-ray scattering (SAXS) data and hydrogen-deuterium exchange followed by mass spectrometry. Here we report that the protein forms dimers in solution with a radius of gyration of 2.9 nm and maximum dimension of 9.0 nm. We also show that the NGFI-B LBD dimer is V-shaped, with the opening angle significantly larger than that of classical dimer's exemplified by estrogen receptor (ER) or retinoid X receptor (RXR). Surprisingly, NGFI-B dimers formation does not occur via the classical nuclear receptor dimerization interface exemplified by ER and RXR, but instead, involves an extended surface area composed of the loop between helices 3 and 4 and C-terminal fraction of the helix 3. Remarkably, the NGFI-B dimer interface is similar to the dimerization interface earlier revealed for glucocorticoid nuclear receptor (GR), which might be relevant to the recognition of cognate DNA response elements by NGFI-B and to antagonism of NGFI-B-dependent transcription exercised by GR in cells. Published by Cold Spring Harbor Laboratory Press. Copyright © 2007 The Protein Society.

Estudio histológico comparativo de la reparación ósea entre hueso alveolar y extra-alveolar en los cerdos sometidos a osteotomía con alta y baja velocidad, con refrigeración líquida

Taking into account the bone repair process in pigs has shown a greater similarity among the histological variables studied compared to other biological models, the present study has as its aim to evaluate the histological bone repair process of osteotomy performed on alveolar and extra-alveolar bones, using drilling tools with liquid refrigeration. Material and method: Eighteen Large White pigs weighing between 20 and 25 Kg were divided into three groups of six animals in order to evaluate the osteotomy repairs with low and high speed in the alveolar bone and threes in the extra-alveolar area, study periods of 7, 14 and 28 days. Results: It was observed that in the alveolar bone at the postoperative times of 14 and 28 days, the best repair results were in the osteotomy performed with low speed, while in the 7 day postoperative period, the results with high speed were slightly better, in alveolar areas as well as extra-alveolar areas. There no statistically significant differences between the alveolar and extra-alveolar bone repair process. Conclusions: The repair process, by means of microscopic analysis in the alveolar and extra-alveolar areas, are similar with better results observed in osteotomies performed with low speed drills in the 14 and 28 day study periods, and at 7 days postoperative the results with high speed drills and refrigeration were slightly better. Research works using pigs as an animal model are perfectly viable. © 2011 SECOM.

Mathematical analysis and simulations involving chemotherapy and surgery on large human tumours under a suitable cell-kill functional response

Dosage and frequency of treatment schedules are important for successful chemotherapy. However, in this work we argue that cell-kill response and tumoral growth should not be seen as separate and therefore are essential in a mathematical cancer model. This paper presents a mathematical model for sequencing of cancer chemotherapy and surgery. Our purpose is to investigate treatments for large human tumours considering a suitable cell-kill dynamics. We use some biological and pharmacological data in a numerical approach, where drug administration occurs in cycles (periodic infusion) and surgery is performed instantaneously. Moreover, we also present an analysis of stability for a chemotherapeutic model with continuous drug administration. According to Norton & Simon [22], our results indicate that chemotherapy is less eficient in treating tumours that have reached a plateau level of growing and that a combination with surgical treatment can provide better outcomes.

Associação entre fatores epidemiológicos e neoplasias mamárias em cadelas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Osteotomia com brocas de alta e baixa rotação, com e sem refrigeração líquida: estudo histopatológico duplo cego em suínos

Pós-graduação em Odontologia - FOA

Otimização e aperfeiçoamento BAC pra estudos envolvendo o trato gastrintestinal

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estabilidade global e bifurcação de Hopf em um modelo de HIV baseado em sistemas do tipo Lotka-Volterra

Pós-graduação em Matematica Aplicada e Computacional - FCT

Reparação óssea após osteotomia com brocas de alta e baixa rotação e refrigeração líquida: estudo histológico comparativo entre tecido ósseo alveolar e extra-alveolar em suínos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise de propriedades mecânicas e microscópicas de um gesso tipo IV após incorporação de derivados da clorexidina

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Rock outcrop orchids reveal the genetic connectivity and diversity of inselbergs of northeastern Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Osteotomia com brocas de alta e baixa rotação, com e sem refrigeração líquida: estudo histopatológico duplo cego em suínos

Nine swines of the White Large race were used for study of the process of bony repair after osteotomy with rotating instruments of low and high-speed, with and without liquid refrigeration. The authors observed, through double blind histopathological analysis, that in every analyzed operative time, the bony repair was processed more appropriately when the osteotomies were accomplished with liquid refrigeration. In the final postoperative times, of fourteen and twenty-eight days, the best results of bony repair were observed in the osteotomy accomplished with drills of low rotation and with liquid refrigeration, while in the postoperative time of seven days, the results of the bony repair of osteotomy accomplished with drills of high rotation and with liquid refrigeration they were better. The authors consider, still, that the process of bony repair in swine display larger proximity in the histological pictures among the studied variables, when compared with other biological models. As most of the works told in the literature it refers the use of dogs, the authors consider that the present work guarantees your importance in the sense of looking for a closer model of the man.

Bayesian L-optimal exact design of experiments for biological kinetic models

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)