Vascular Endothelial Growth Factor Expression in Invasive Papillary Thyroid Carcinoma

Background: The vascular endothelial growth factor (VEGF) is a major promoter of endothelial growth and migration. Some studies have shown a correlation between expression of this growth factor and prognosis in several cancers, including well-differentiated thyroid cancer. Aim: We studied VEGF expression, local invasiveness, and other prognostic factors in papillary thyroid carcinoma (PTC) to test the hypothesis that the expression of VEGF is correlated with the degree of invasion of PTC. Patients and Methods: Clinical and pathological data of 76 patients with PTC were retrospectively reviewed. Group 1 consisted of patients with gross locally invasive tumors, group 2 consisted of patients with only invasion of the thyroid capsule, and group 3 consisted of patients with noninvasive PTC. Results: VEGF expression was noted within the tumor in all groups of PTC patients but was absent in the surrounding normal tissue. Older patients had higher expression of VEGF than younger patients. The age of patients with strong reaction to VEGF was 46 +/- 14 (mean +/- standard deviation), and that in patients with a weaker reaction was 39 +/- 16 (p<0.05). Only 20% of patients with a follicular variant of PTC had a strong reaction to VEGF compared with 68% of patients with classical PTC (p<0.01). Conclusions: VEGF expression appears to be an early event in the development of PTC. Whether VEGF expression promotes the progression of PTC is not known, but the answer to this question may be important in view of its greater expression in older patients, a group whose prognosis in PTC is worse.

Two successful pregnancies in a woman with chronic myeloid leukemia exposed to nilotinib during the first trimester of her second pregnancy: case study

The occurrence of chronic myeloid leukemia in pregnancy is rare and its management poses a clinical challenge for physicians treating these patients. We report a 30-year-old woman with chronic myeloid leukemia who became pregnant twice successfully. Philadelphia-positive CML in its chronic phase was diagnosed at 16 weeks of her first gestation. At that time, she received no treatment throughout her pregnancy. At 38 weeks of gestation, a normal infant was delivered by cesarean section. At six weeks postpartum, the patient underwent imatinib mesylate therapy but she could not tolerate the treatment. The treatment was then changed to nilotinib at 400 mg orally b.i.d. Two years later, she became pregnant again while she was on nilotinib 200 mg b.i.d. The unplanned pregnancy was identified during her 7.4 weeks of gestation. Because the patient elected to continue her pregnancy, nilotinib was stopped immediately, and no further treatment was given until delivery. Neither obstetrical complications nor structural malformations in neonates in both pregnancies were observed. Both babies' growth and development have been normal. Although this experience is limited to a single patient, the success of this patient demonstrates that the management of chronic myeloid leukemia in pregnant women may be individualized based on the relative risks and benefits of the patient and fetus.

Latin American Consensus: Children Born Small for Gestational Age

Background: Children born small for gestational age (SGA) experience higher rates of morbidity and mortality than those born appropriate for gestational age. In Latin America, identification and optimal management of children born SGA is a critical issue. Leading experts in pediatric endocrinology throughout Latin America established working groups in order to discuss key challenges regarding the evaluation and management of children born SGA and ultimately develop a consensus statement. Discussion: SGA is defined as a birth weight and/or birth length greater than 2 standard deviations (SD) below the population reference mean for gestational age. SGA refers to body size and implies length-weight reference data in a geographical population whose ethnicity is known and specific to this group. Ideally, each country/region within Latin America should establish its own standards and make relevant updates. SGA children should be evaluated with standardized measures by trained personnel every 3 months during year 1 and every 6 months during year 2. Those without catch-up growth within the first 6 months of life need further evaluation, as do children whose weight is <= -2 SD at age 2 years. Growth hormone treatment can begin in SGA children > 2 years with short stature (< -2.0 SD) and a growth velocity < 25th percentile for their age, and should continue until final height (a growth velocity below 2 cm/year or a bone age of > 14 years for girls and > 16 years for boys) is reached. Blood glucose, thyroid function, HbA1c, and insulin-like growth factor-1 (IGF-1) should be monitored once a year. Monitoring insulin changes from baseline and surrogates of insulin sensitivity is essential. Reduced fetal growth followed by excessive postnatal catch-up in height, and particularly in weight, should be closely monitored. In both sexes, gonadal function should be monitored especially during puberty. Summary: Children born SGA should be carefully followed by a multidisciplinary group that includes perinatologists, pediatricians, nutritionists, and pediatric endocrinologists since 10% to 15% will continue to have weight and height deficiency through development and may benefit from growth hormone treatment. Standards/guidelines should be developed on a country/region basis throughout Latin America.

Expression and cellular localization of microRNA-29b and RAX, an activator of the RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced diabetic rats

Purpose: The apoptosis of retinal neurons plays a critical role in the pathogenesis of diabetic retinopathy (DR), but the molecular mechanisms underlying this phenomenon remain unclear. The purpose of this study was to investigate the cellular localization and the expression of microRNA-29b (miR-29b) and its potential target PKR associated protein X (RAX), an activator of the pro-apoptotic RNA-dependent protein kinase (PKR) signaling pathway, in the retina of normal and diabetic rats. Methods: Retinas were obtained from normal and diabetic rats within 35 days after streptozotocin (STZ) injection. In silico analysis indicated that RAX is a potential target of miR-29b. The cellular localization of miR-29b and RAX was assessed by in situ hybridization and immunofluorescence, respectively. The expression levels of miR-29b and RAX mRNA were evaluated by quantitative reverse transcription PCR (qRT-PCR), and the expression of RAX protein was evaluated by western blot. A luciferase reporter assay and inhibition of endogenous RAX were performed to confirm whether RAX is a direct target of miR-29b as predicted by the in silico analysis. Results: We found that miR-29b and RAX are localized in the retinal ganglion cells (RGCs) and the cells of the inner nuclear layer (INL) of the retinas from normal and diabetic rats. Thus, the expression of miR-29b and RAX, as assessed in the retina by quantitative RT-PCR, reflects their expression in the RGCs and the cells of the INL. We also revealed that RAX protein is upregulated (more than twofold) at 3, 6, 16, and 22 days and downregulated (70%) at 35 days, whereas miR-29b is upregulated (more than threefold) at 28 and 35 days after STZ injection. We did not confirm the computational prediction that RAX is a direct target of miR-29b. Conclusions: Our results suggest that RAX expression may be indirectly regulated by miR-29b, and the upregulation of this miRNA at the early stage of STZ-induced diabetes may have a protective effect against the apoptosis of RGCs and cells of the INL by the pro-apoptotic RNA-dependent protein kinase (PKR) signaling pathway.

Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth

Background: Human Papillomavirus, HPV, is the main etiological factor for cervical cancer. Different studies show that in women infected with HPV there is a positive correlation between lesion grade and number of infiltrating macrophages, as well as with IL-10 higher expression. Using a HPV16 associated tumor model in mice, TC-1, our laboratory has demonstrated that tumor infiltrating macrophages are M2-like, induce T cell regulatory phenotype and play an important role in tumor growth. M2 macrophages secrete several cytokines, among them IL-10, which has been shown to play a role in T cell suppression by tumor macrophages in other tumor models. In this work, we sought to establish if IL-10 is part of the mechanism by which HPV tumor associated macrophages induce T cell regulatory phenotype, inhibiting anti-tumor activity and facilitating tumor growth. Results: TC-1 tumor cells do not express or respond to IL-10, but recruit leukocytes which, within the tumor environment, produce this cytokine. Using IL-10 deficient mice or blocking IL-10 signaling with neutralizing antibodies, we observed a significant reduction in tumor growth, an increase in tumor infiltration by HPV16 E7 specific CD8 lymphocytes, including a population positive for Granzyme B and Perforin expression, and a decrease in the percentage of HPV specific regulatory T cells in the lymph nodes. Conclusions: Our data shows that in the HPV16 TC-1 tumor mouse model, IL-10 produced by tumor macrophages induce regulatory phenotype on T cells, an immune escape mechanism that facilitates tumor growth. Our results point to a possible mechanism behind the epidemiologic data that correlates higher IL-10 expression with risk of cervical cancer development in HPV infected women.

Expression of recombinant Araraquara Hantavirus nucleoprotein in insect cells and its use as an antigen for immunodetection compared to the same antigen expressed in Escherichia coli

Background: Antigens for Hantavirus serological tests have been produced using DNA recombinant technology for more than twenty years. Several different strategies have been used for that purpose. All of them avoid the risks and difficulties involved in multiplying Hantavirus in the laboratory. In Brazil, the Araraquara virus is one of the main causes of Hantavirus Cardio-Pulmonary Syndrome (HCPS). Methods: In this investigation, we report the expression of the N protein of the Araraquara Hantavirus in a Baculovirus Expression System, the use of this protein in IgM and IgG ELISA and comparison with the same antigen generated in E. coli. Results: The protein obtained, and purified in a nickel column, was effectively recognized by antibodies from confirmed HCPS patients. Comparison of the baculovirus generated antigen with the N protein produced in E. coli showed that both were equally effective in terms of sensitivity and specificity. Conclusions: Our results therefore indicate that either of these proteins can be used in serological tests in Brazil.

Interethnic Differences in the Distribution of Clinically Relevant Vascular Endothelial Growth Factor Genetic Polymorphisms

Vascular endothelial growth factor (VEGF) is a homodimeric glycoprotein produced mostly in endothelial cells and its transcription is regulated by a variety of growth factors and cytokines. VEGF plays many relevant roles, and three functional polymorphisms in the promoter region of the VEGF gene (C-2578A, G-1154A, and G-634C) have been associated with disease conditions. Although some studies suggest that interethnic differences exist in the distribution of these variants, no previous study has examined this hypothesis in admixed populations. We examined the distribution of these three clinically relevant VEGF single-nucleotide polymorphisms in 175 white and 185 black subjects. We have also estimated the haplotype distribution and assessed associations between these variants. Although the A-2578 and A-1154 variants were more common in whites (39% and 29%, respectively) than in blacks (29% and 16%, respectively; both p < 0.05), no significant interethnic differences were found with regards to the G-634C polymorphism. While the haplotype including the C-2578, G-1154, and G-634 variants was the most common in both ethnic groups, it was more common in blacks than in whites (p < 0.05). The haplotype including the C-2578, A-1154, and G-634 alleles and the haplotype including the C-2578, A-1154, and C-634 alleles were more common in whites than in blacks (both p < 0.05). These results show marked interethnic differences in the distribution of genetic variants of VEGF that may explain, at least in part, interethnic disparities in the susceptibility to cardiovascular diseases.

Viral mutation and its influence in the time evolution of the immunizations

In this paper, we study the behavior of immune memory against antigenic mutation. Using a dynamic model proposed by one of the authors in a previous study (A. de Castro [Phys. J. Appl. Phys. 33, 147 (2006) and Simul. Mod. Pract. Theory. 15, 831 (2007)]), we have performed simulations of several inoculations, where in each virtual sample the viral population undergoes mutations. Our results suggest that the sustainability of the immunizations is dependent on viral variability and that the memory lifetimes are not random, what contradicts what was suggested by Tarlinton et al. [Curr. Opin. Immunol. 20, 162 (2008)]. We show that what may cause an apparent random behavior of the immune memory is the antigenic variability.

New Epidemiological Data on Brazilian Spotted Fever in an Endemic Area of the State of Sao Paulo, Brazil

The present work evaluated rickettsial infection in dogs and their ticks in an area endemic for Brazilian spotted fever (BSF) in the metropolitan area of Sao Paulo, Brazil, where the tick Amblyomma aureolatum was presumed to be the vector of the disease. Ticks were collected on dogs from 185 houses, encompassing single infestations by Rhipicephalus sanguineus, Amblyomma aureolatum, Amblyomma longirostre, or Amblyomma sp. in dogs from 60 (32.4%), 77 (41.6%), 2 (1.1%), and 25 (13.5%) houses, respectively; 19 (10.3%) houses had dogs with mixed infestations by R. sanguineus and A. aureolatum; 1 (0.5%) house had dogs with infestations by A. aureolatum and A. longirostre; and 1 (0.5%) house had dogs with infestations by R. sanguineus and Amblyomma sp. Overall, A. aureolatum was present in dogs from 97 (52.4%) houses, and R. sanguineus in dogs from 80 (43.2%) houses. A total of 287 ticks (130 A. aureolatum and 157 R. sanguineus) infesting dogs from 98 houses were selected for testing by polymerase chain reaction (PCR) targeting rickettsial genes. Overall, 3.1% of the A. aureolatum ticks were infected by Rickettsia bellii, and 1.3% of the R. sanguineus were infected by Ricketttsii rickettsii. For serology, we selected 23 dogs living in and in the vicinity of the house where the R. rickettsii-infected ticks were collected. The indirect fluorescent antibody (IFA) test detected antibodies reactive with R. rickettsii in sera from 16 (69.6%) dogs, with titers ranging from 256 to 32,768. It is established that Amblyomma aureolatum is a vector of R. rickettsii in the Sao Paulo metropolitan area, but our results highlight for the first time in Brazil, a possible role of R. sanguineus in the epidemiology of R. rickettsii, corroborating previous findings in Mexico and the United States, where R. sanguineus has been implicated in the transmission of R. rickettsii to humans.

Evaluation of the Bond Strength Between a Composite Resin and Enamel Submitted to Bleaching Treatment and Etched with Er:YAG Laser

Background: The use of laser irradiation for dental surface treatment may increase tooth-composite bond strength. Its use on bleached teeth may decrease the waiting time between bleaching and restorative procedures. Objective: This study aimed to evaluate the bond strength between a composite resin and bovine enamel bleached with 35% hydrogen peroxide and etched with Er:YAG laser. Materials and Methods: Thirty bovine teeth were randomly divided into six groups (n = 5): G1, unbleached and restored 24 h after storage in artificial saliva, etching with 35% phosphoric acid (PA) (control); G2, unbleached and restored 24 h after storage in artificial saliva, etching with Er:YAG laser and 35% PA; G3, bleached and restored immediately afterward, etching with 35% PA; G4, bleached and restored 24 h after bleaching, etching with 35% PA; G5, bleached and restored immediately afterward, etching with Er:YAG and 35% PA laser; G6, bleached and restored 24 h after bleaching, etching with Er:YAG laser and 35% PA. Bond strength was quantitatively evaluated by microtensile test (1.0 mm/min). Data were submitted to statistical analysis using ANOVA and Tukey tests (alpha - 0.05). Results: Bond strength values (MPa) were G1, 26.17 +/- 4.44; G2, 28.87 +/- 3.94; G3, 17.25 +/- 4.58; G4, 21.93 +/- 5.02; G5, 16.69 +/- 2.31; and G6, 29.06 +/- 8.31. There was no statistically significant difference among groups G1, G2, and G6 (p - 0.119), which presented higher bond strength than group G4, followed by groups G3 and G5. Conclusion: Er:YAG irradiation of bleached surfaces may favor bonding procedures when performed 24 h after bleaching.

Viability of fibroblasts cultured under nutritional stress irradiated with red laser, infrared laser, and red light-emitting diode

Phototherapy is noninvasive, painless and has no known side effect. However, for its incorporation into clinical practice, more well-designed studies are necessary to define optimal parameters for its application. The viability of fibroblasts cultured under nutritional stress irradiated with either a red laser, an infrared laser, or a red light-emitting diode (LED) was analyzed. Irradiation parameters were: red laser (660 nm, 40 mW, 1 W/cm(2)), infrared laser (780 nm, 40 mW, 1 W/cm(2)), and red LED (637 +/- 15 nm, 40 mW, 1 W/cm(2)). All applications were punctual and performed with a spot with 0.4 mm(2) of diameter for 4 or 8 s. The Kruskal-Wallis test and analysis of variance of the general linear model (p <= 0.05) were used for statistical analysis. After 72 h, phototherapy with low-intensity laser and LED showed no toxicity at the cellular level. It even stimulated methylthiazol tetrazolium assay (MTT) conversion and neutral red uptake of fibroblasts cultured under nutritional stress, especially in the group irradiated with infrared laser (p = 0.004 for MTT conversion and p < 0.001 for neutral red uptake). Considering the parameters and protocol of phototherapy used, it can be concluded that phototherapy stimulated the viability of fibroblasts cultured under nutritional deficit resembling those found in traumatized tissue in which cell viability is reduced. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3602850]

Additive genetic relationship of longevity with fertility and production traits in Nellore cattle based on bivariate models

Survival or longevity is an economically important trait in beef cattle. The main inconvenience for its inclusion in selection criteria is delayed recording of phenotypic data and the high computational demand for including survival in proportional hazard models. Thus, identification of a longevity-correlated trait that could be recorded early in life would be very useful for selection purposes. We estimated the genetic relationship of survival with productive and reproductive traits in Nellore cattle, including weaning weight (WW), post-weaning growth (PWG), muscularity (MUSC), scrotal circumference at 18 months (SC18), and heifer pregnancy (HP). Survival was measured in discrete time intervals and modeled through a sequential threshold model. Five independent bivariate Bayesian analyses were performed, accounting for cow survival and the five productive and reproductive traits. Posterior mean estimates for heritability (standard deviation in parentheses) were 0.55 (0.01) for WW, 0.25 (0.01) for PWG, 0.23 (0.01) for MUSC, and 0.48 (0.01) for SC18. The posterior mean estimates (95% confidence interval in parentheses) for the genetic correlation with survival were 0.16 (0.13-0.19), 0.30 (0.25-0.34), 0.31 (0.25-0.36), 0.07 (0.02-0.12), and 0.82 (0.78-0.86) for WW, PWG, MUSC, SC18, and HP, respectively. Based on the high genetic correlation and heritability (0.54) posterior mean estimates for HP, the expected progeny difference for HP can be used to select bulls for longevity, as well as for post-weaning gain and muscle score.

NGC 7097: THE ACTIVE GALACTIC NUCLEUS AND ITS MIRROR, REVEALED BY PRINCIPAL COMPONENT ANALYSIS TOMOGRAPHY

Three-dimensional spectroscopy techniques are becoming more and more popular, producing an increasing number of large data cubes. The challenge of extracting information from these cubes requires the development of new techniques for data processing and analysis. We apply the recently developed technique of principal component analysis (PCA) tomography to a data cube from the center of the elliptical galaxy NGC 7097 and show that this technique is effective in decomposing the data into physically interpretable information. We find that the first five principal components of our data are associated with distinct physical characteristics. In particular, we detect a low-ionization nuclear-emitting region (LINER) with a weak broad component in the Balmer lines. Two images of the LINER are present in our data, one seen through a disk of gas and dust, and the other after scattering by free electrons and/or dust particles in the ionization cone. Furthermore, we extract the spectrum of the LINER, decontaminated from stellar and extended nebular emission, using only the technique of PCA tomography. We anticipate that the scattered image has polarized light due to its scattered nature.

Fossil groups in the Millennium simulation Their environment and its evolution

Context. Fossil systems are defined to be X- ray bright galaxy groups ( or clusters) with a two- magnitude difference between their two brightest galaxies within half the projected virial radius, and represent an interesting extreme of the population of galaxy agglomerations. However, the physical conditions and processes leading to their formation are still poorly constrained. Aims. We compare the outskirts of fossil systems with that of normal groups to understand whether environmental conditions play a significant role in their formation. We study the groups of galaxies in both, numerical simulations and observations. Methods. We use a variety of statistical tools including the spatial cross- correlation function and the local density parameter Delta(5) to probe differences in the density and structure of the environments of "" normal"" and "" fossil"" systems in the Millennium simulation. Results. We find that the number density of galaxies surrounding fossil systems evolves from greater than that observed around normal systems at z = 0.69, to lower than the normal systems by z = 0. Both fossil and normal systems exhibit an increment in their otherwise radially declining local density measure (Delta(5)) at distances of order 2.5 r(vir) from the system centre. We show that this increment is more noticeable for fossil systems than normal systems and demonstrate that this difference is linked to the earlier formation epoch of fossil groups. Despite the importance of the assembly time, we show that the environment is different for fossil and non- fossil systems with similar masses and formation times along their evolution. We also confirm that the physical characteristics identified in the Millennium simulation can also be detected in SDSS observations. Conclusions. Our results confirm the commonly held belief that fossil systems assembled earlier than normal systems but also show that the surroundings of fossil groups could be responsible for the formation of their large magnitude gap.

Discovery of VVV CL001 A low-mass globular cluster next to UKS 1 in the direction of the Galactic bulge

Context. It is not known how many globular clusters may remain undetected towards the Galactic bulge. Aims. One of the aims of the VISTA Variables in the Via Lactea (VVV) Survey is to accurately measure the physical parameters of the known globular clusters in the inner regions of the Milky Way and search for new ones, hidden in regions of large extinction. Methods. From deep near-infrared images, we derive deep JHK(S)-band photometry of a region surrounding the known globular cluster UKS 1 and reveal a new low-mass globular cluster candidate that we name VVV CL001. Results. We use the horizontal-branch red clump to measure E(B-V) similar to 2.2 mag, (m - M)(0) = 16.01 mag, and D = 15.9 kpc for the globular cluster UKS 1. On the basis of near-infrared colour-magnitude diagrams, we also find that VVV CL001 has E(B-V) similar to 2.0, and that it is at least as metal-poor as UKS 1, although its distance remains uncertain. Conclusions. Our finding confirms the previous projection that the central region of the Milky Way harbours more globular clusters. VVV CL001 and UKS 1 are good candidates for a physical cluster binary, but follow-up observations are needed to decide if they are located at the same distance and have similar radial velocities.