Enhanced sensitivity to rapamycin following long-term oestrogen deprivation in MCF-7, T-47-D and ZR-75-1 human breast cancer cells

Human breast cancer cells (MCF-7, T-47-D and ZR-75-1) can adapt to circumvent any reduced growth rate during long-term oestrogen deprivation, and this provides three model systems to investigate mechanisms of endocrine resistance in breast cancer. In this paper we report consistent differences in the effects of three growth inhibitors following long-term oestrogen deprivation in all three cell models. Long-term oestrogen deprivation of MCF-7, T-47-D and ZR-75-1 cells resulted in reduced growth inhibition by PD98059 (2–10 µg/ml), implying a loss of dependence on mitogen-activated protein kinase pathways for growth. The growth inhibitor LY294002 (2–10 µM) inhibited growth of both oestrogen-maintained and oestrogen-deprived cells with similar dose–responses, implying continued similar dependence on phosphoinositide 3-kinase (PI3K) pathways with no alteration after adaptation to oestrogen independent growth. However, by contrast, long-term oestrogen deprivation resulted in an increased sensitivity to growth inhibition by rapamycin, which was not reduced by readdition of oestradiol. The enhanced inhibition of long-term oestrogen-deprived MCF-7-ED, T-47-D-ED and ZR-75-1-ED cell growth by combining rapamycin with LY294002 at concentrations where each alone had little effect, offers preclinical support to the development of therapeutic combinations of rapamycin analogues with other PI3K inhibitors in endocrine-resistant breast cancer.

RNA interference suppression of genes in glycosyl transferase families 43 and 47 in wheat starchy endosperm causes large decreases in arabinoxylan content

The cell walls of wheat (Triticum aestivum) starchy endosperm are dominated by arabinoxylan (AX), accounting for 65% to 70% of the polysaccharide content. Genes within two glycosyl transferase (GT) families, GT43 (IRREGULAR XYLEM9 [IRX9] and IRX14) and GT47 (IRX10), have previously been shown to be involved in the synthesis of the xylan backbone in Arabidopsis, and close homologs of these have been implicated in the synthesis of xylan in other species. Here, homologs of IRX10 TaGT47_2 and IRX9 TaGT43_2, which are highly expressed in wheat starchy endosperm cells, were suppressed by RNA interference (RNAi) constructs driven by a starchy endosperm-specific promoter. The total amount of AX was decreased by 40% to 50% and the degree of arabinosylation was increased by 25% to 30% in transgenic lines carrying either of the transgenes. The cell walls of starchy endosperm in sections of grain from TaGT43_2 and TaGT47_2 RNAi transgenics showed decreased immunolabeling for xylan and arabinoxylan epitopes and approximately 50% decreased cell wall thickness compared with controls. The proportion of AX that was water soluble was not significantly affected, but average AX polymer chain length was decreased in both TaGT43_2 and TaGT47_2 RNAi transgenics. However, the long AX chains seen in controls were absent in TaGT43_2 RNAi transgenics but still present in TaGT47_2 RNAi transgenics. The results support an emerging picture of IRX9-like and IRX10-like proteins acting as key components in the xylan synthesis machinery in both dicots and grasses. Since AX is the main component of dietary fiber in wheat foods, the TaGT43_2 and TaGT47_2 genes are of major importance to human nutrition.

Histopathology and laser autofluorescence of ischemic kidneys of rats

The purpose of this research was to evaluate the severity of renal ischemia/reperfusion injury as determined by histology and by laser-induced fluorescence (LIF) with excitation wavelengths of 442 nm and 532 nm. Wistar rats (four groups of six animals) were subjected to left renal warm ischemia for 20, 40, 60 and 80 min followed by 10 min of reperfusion. Autofluorescence was determined before ischemia (control) and then every 5-10 min thereafter. Tissue samples for histology were harvested from the right kidney (control) and from the left kidney after reperfusion. LIF and ischemia time showed a significant correlation (p < 0.0001 and r (2)=0.47, and p=0.006 and r (2)=0.25, respectively, for the excitation wavelengths of 442 nm and 532 nm). Histological scores showed a good correlation with ischemia time (p < 0.0001). The correlations between optical spectroscopy values and histological damage were: LIF at 442 nm p < 0.0001, LIF at 532 nm p=0.001; IFF (peak of back scattered light/LIF) at 442 nm p > 0.05, and IFF at 532 nm p > 0.05. After reperfusion LIF tended to return to preischemic basal levels which occurred in the presence of histological damage. This suggests that factors other than morphological alterations may have a more relevant effect on changes observed in LIF. In conclusion, renal ischemia/reperfusion changed tissue fluorescence induced by laser. The excitation light of 442 nm showed a better correlation with the ischemia time and with the severity of tissue injury.

Evidence for the monoclinic-tetragonal phase coexistence in Pb(Zr(0.53)Ti(0.47))O(3) thin films

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

Eficácia da N-butilescopolamina e dipirona sódica associadas ao cetoprofeno no alívio da dor pós-operatória de pacientes submetidas a duas técnicas diferentes de laqueadura por laparoscopia

JUSTIFICATIVA E OBJETIVOS: A laqueadura laparoscópica (LL) é um dos procedimentos mais dolorosos e a intensidade da dor varia com a técnica selecionada, sendo mais intensa com a técnica de oclusão das tubas uterinas com anel. As pacientes submetidas à LL referem dor em cólica no período PO e a N-butilescopolamina e a dipirona sódica, por suas propriedades anti-espasmódicas e analgésicas, associadas às propriedades antiinflamatórias do cetoprofeno, podem ser opção para profilaxia e tratamento de dor. O objetivo deste foi estudar a eficácia da N-butilescopolamina e da dipirona sódica associadas ao cetoprofeno, na prevenção de dor PO em pacientes submetidas à LL, com duas técnicas diferentes - diatermia e pinçamento com anel. MÉTODO: Participaram do estudo 50 pacientes, estado físico ASA I e II, com idade entre 23 e 47 anos. As pacientes foram distribuídas aleatoriamente em dois grupos: G1 - oclusão das tubas uterinas com anéis, G2 - oclusão das tubas uterinas com diatermia. Todas as pacientes receberam N-butilescopolamina (20 mg) e dipirona sódica (2500 mg) e cetoprofeno (100 mg), por via venosa, imediatamente antes da indução da anestesia. A dor foi avaliada pelo critério de escala numérica verbal, variando de 0 a 10, sendo 0 ausência de dor e 10 o máximo de dor, a cada 10 minutos na primeira hora, na sala de recuperação pós-anestésica (SRPA) e na 1ª, 2ª, 3ª e 4ª horas após a alta da SRPA. Dor com intensidade maior que 3 era tratada com tramadol (100 mg), por via venosa. A avaliação da dor foi realizada sem que se soubesse a que grupo pertencia a paciente. Para análise estatística, testes t de Student, Mann-Whitney e Friedman. RESULTADOS: Ambos os grupos foram idênticos com relação à idade, ao peso, à altura, à duração da cirurgia e anestesia. As pacientes do G1 apresentaram maior escore de dor que as do G2, em todos os momentos do estudo. Valores estatisticamente significativos: 80% das pacientes de G1 e 16% de G2 necessitaram de tramadol em algum momento do estudo. CONCLUSÕES: A N-butilescopolamina e a dipirona sódica associadas ao cetoprofeno mostraram ser alternativa de analgesia pós-operatória quando a laqueadura é realizada com a técnica de diatermia.

Ultrastructural features of myenteric ganglia of adult Wistar rats (Rattus norvegicus)

The ultrastructural features of the ganglia of the myenteric plexus exhibit changes according to the animal species. These myenteric ganglia in the duodenum of adult rats of the Wistar strain were characterized ultrastructurally in this work. Those ganglia were depicted as compact structures, composed of neurones and glial cells, forming a dense neuropil surrounded by a continuous basal lamina and collagen fibrils. Glial cell bodies were smaller and apparently more frequent than neuronal cell bodies, being morphologically distinguished by nuclear features. In the neuronal extensions granular and agranular synaptic vesicles of different sizes predominate, in addition to mitochondria and myelinized profiles. Gliofilaments were not observed on the glial extensions of the rats.

Epidemiological aspects of enteroparasitosis at daycare centers in the city of Botucatu, State of São Paulo, Brazil

Estimou-se a prevalência e a incidência de parasitas intestinais em crianças e funcionários de 5 creches municipais em Botucatu/SP. Foram realizados dois estudos seccionais em 2002 (N=379) e 2003 (N=397) e um estudo longitudinal observacional, onde as crianças de 2002 e 2003 foram seguidas por um ano. Foram aplicados questionários nos funcionários e nos pais das crianças, onde foram coletadas as seguintes variáveis: nível sócio-econômico, hábitos sanitários, moradia, idade, sexo e presença de animais domésticos. Foram realizados exames coproparasitológicos nas crianças das creches. A prevalência de enteroparasitas em 2002 foi de 76,74% e 34% em 2003. As variáveis associadas à presença de enteroparasitas no ano de 2002 foram: localização das creches (OR=0,27 IC=0,15-0,47), renda familiar (OR=4,38 IC=1,91-10,04), sexo (OR=0,52 IC=0,32-0,85), faixa etária (OR=2,08 IC=1,06-4,08) e presença de animais domésticos na casa (OR=1,85 IC=1,10-3,11); em 2003, as variáveis foram: creche localizada em bairro periférico (OR=0,49 IC=0,31-0,78), renda familiar (OR=3,69 IC=2,19-6,24), nível educacional da mãe (OR=6,19 IC=1,81-21,21), sexo (OR=0,36 IC=0,36-0,93) e presença de animais domésticos (OR=1,68 IC=1,01-2,79). A coorte foi integrada por 253 crianças apresentando incidência de 23,22%. Os dados deste estudo evidenciam situações de risco em populações específicas (creches) e poderiam ser utilizados por Instituições que promovem o cuidado com as crianças.

Synthesis and electrical characterization of tungsten doped Pb(Zr0.53Ti0.47)O-3 ceramics obtained from a hybrid process

Pure and W-doped PZT ceramics (PZT and PZTW) were prepared by a hybrid process consisting in the association of polymeric precursor and partial oxalate methods. The phase formation was investigated by simultaneous thermal analysis (TG/DSC) and X-ray diffraction (XRD). The effect of W doping PZT and their electrical properties was evaluated. Substitution of W by Ti leads to an increase of Curie temperature and broadening of dielectric constant. A typical hysteresis loop was observed at room temperature and the remnant polarization was increased with the content of W. (c) 2007 Elsevier B.V. All rights reserved.

Dielectric and fatigue properties of Pb(Zr0.53Ti0.47)O-3 thin films prepared from oxide precursors method

Fatigue is an important problem to be considered if a ferroelectric film is used for non-volatile memory devices. In this phenomena, the remanent polarization and coercive field properties degrades in cycles which increase in hysteresis loops. The reasons have been attributed to different mechanisms such as a large voltage applied on ferroelectric film in every reading process in Ferroelectric Random Access Memory (FeRAM) or memories for digital storage in computer, grain size effects and others. The aim of this work is to investigate the influence of the crystallization kinetics on dielectric and ferroelectric properties of the Pb(Zr0.53Ti0.47)O-3 thin films prepared by an alternative chemical method. Films were crystallized in air on Pt/Ti/SiO2/Si substrates at 700 degrees C for 1 hour, in conventional thermal annealing (CTA), and at 700 degrees C for 1 min and 700 degrees C 5 min, using a rapid thermal annealing (RTA) process. Final films were crack free and presented an average of 750 nm in thickness. Dielectric properties were studied in the frequency range of 100 Hz - 1 MHz. All films showed a dielectric dispersion at low frequency. Ferroelectric properties were measured from hysteresis loops at 10 kHz. The obtained remanent polarization (P-r) and coercive field (E-c) were 3.7 mu C/cm(2) and 71.9 kV/cm respectively for film crystallized by CTA while in films crystallized by RTA these parameters were essentially the same. In the fatigue process, the P, value decreased to 14% from the initial value after 1.3 x 10(9) switching cycles, for film by CTA, while for film crystallized by RTA for 5 min, P, decreased to 47% from initial value after 1.7 x 10(9) switching cycles.

Meta-análise de parâmetros genéticos relacionados ao consumo alimentar residual e a suas características componentes em bovinos

The objective of this work was to estimate, by meta-analysis, the heritability (h(2)) and the genetic (r(g)) and phenotypic (r(f)) correlations of residual feed intake (RFI), and of its component traits in beef cattle from 19 breeds or genetic groups. Twenty-two scientific papers published from 1963 to 2011, from eight countries, totaling 52,637 cattle of ages from 28 days up to slaughter, were evaluated. The estimates of RFI, dry matter intake (DMI), average daily gain (ADG) and metabolic weight (BW0.75) were weighted by the inverse of sample variance. The variation between studies of h(2) for each trait was analyzed by weighted least squares. The effects of sex, country and breed were significant for h(2) of RFI, explaining 67% of variation between studies. For DMI, country and breed effects were significant and explained 96% of variation. Pooled estimates of h(2) were: 0.255+/-0.008, 0.278+/-0.012, 0.321+/-0.015, and 0.397+/-0.032 for RFI, DMI, ADG and BW0.75, respectively. Pooled estimates of genetic and phenotypic correlations were low between RFI and ADG and between RFI and BW0.75 (from -0.021+/-0.034 to 0.025+/-0.035), and moderate between RFI and DMI (0.636+/-0.035 and 0.698+/-0.041) and between DMI, ADG and BW0.75 (0.441+/-0.062 to 0.688+/-0.032). The trait RFI has lower heritability estimates than its components.