Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor.

PURPOSE: Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) was used to evaluate treatment response in patients with gastrointestinal stromal tumors (GIST) after administration of sunitinib, a multitargeted tyrosine kinase inhibitor, after imatinib failure. PATIENTS AND METHODS: Tumor metabolism was assessed with FDG-PET before and after the first 4 weeks of sunitinib therapy in 23 patients who received one to 12 cycles of sunitinib therapy (4 weeks of 50 mg/d, 2 weeks off). Treatment response was expressed as the percent change in maximal standardized uptake values (SUV). The primary end point of time to tumor progression was compared with early PET results on the basis of traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Progression-free survival (PFS) was correlated with early FDG-PET metabolic response (P < .0001). Using -25% and +25% thresholds for SUV variations from baseline, early FDG-PET response was stratified in metabolic partial response, metabolically stable disease, or metabolically progressive disease; median PFS rates were 29, 16, and 4 weeks, respectively. Similarly, when a single FDG-PET positive/negative was considered after 4 weeks of sunitinib, the median PFS was 29 weeks for SUVs less than 8 g/mL versus 4 weeks for SUVs of 8 g/mL or greater (P < .0001). None of the patients with metabolically progressive disease subsequently responded according to RECIST criteria. Multivariate analysis showed shorter PFS in patients who had higher residual SUVs (P < .0001), primary resistance to imatinib (P = .024), or nongastric GIST (P = .002), regardless of the mutational status of the KIT and PDGFRA genes. CONCLUSION: Week 4 FDG-PET is useful for early assessment of treatment response and for the prediction of clinical outcome. Thus, it offers opportunities to individualize and optimize patient therapy.

Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry.

BACKGROUND: Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. METHODS: 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow-up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analysed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40 ng/ml during 12 months of follow-up and several dosage regimens were evaluated by simulation. RESULTS: A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/ritonavir and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the inter-individual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates, and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300,000 IU two times per year. CONCLUSIONS: This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

2,4-dichlorophenoxyacetic acid as an alternative auxin for rooting of vine rootstock cuttings

Viticulture is an important agricultural activity in semiarid northeastern Brazil, and the quality and ease of vine propagation are very important in this context. This study evaluated the use of 2,4-dichlorophenoxyacetic acid (2,4-D) as an alternative to indolebutyric acid (IBA) in the rooting of vine rootstock cuttings. The trial was conducted at the Universidade Federal de Sergipe (São Cristóvão-SE) between January and March 2010 with cuttings of the rootstocks of 'IAC-766', 'IAC-572', and 'Paulsen 1103' treated with 2,4-D or IBA applied at concentrations of 0, 1000, 2000, or 3000 rng-L-1 for 5 s and planted in a field on washed sand. At 56 days after planting, the percentages of rooted, sprouted, callused, and dead cuttings were evaluated, and also the average number and length of the rooted cuttings. The results showed that 2,4-D was not superior to IBA in the characteristics wanted for the rooting process of the vine rootstock cuttings. The vine rootstocks showed potential for propagation by cutting without auxin application. It was observed that the high concentrations were the worst for the rooting of the cuttings.

Study of D J meson decays to D +π-, D 0π+ and D ∗+π- final states in pp collisions

A study of D +π−, D 0π+ and D ∗+π− final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fb−1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D 1(2420)0 resonance is observed in the D ∗+π− final state and the D∗2(2460) resonance is observed in the D +π−, D 0π+ and D ∗+π− final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the D ∗+π−, D +π− and D 0π+ final states.

Is altitude training an efficient treatment for obesity?

Worldwide, about half the adult population is considered overweight as defined by a body mass index (BMI - calculated by body weight divided by height squared) ratio in excess of 25 kg.m-2. Of these individuals, half are clinically obese (with a BMI in excess of 30) and these numbers are still increasing, notably in developing countries such as those of the Middle East region. Obesity is a disorder characterised by increased mass of adipose tissue (excessive fat accumulation) that is the result of a systemic imbalance between food intake and energy expenditure. Although factors such as family history, sedentary lifestyle, urbanisation, income and family diet patterns determine obesity prevalence, the main underlying causes are poor knowledge about food choice and lack of physical activity3. Current obesity treatments include dietary restriction, pharmacological interventions and ultimately, bariatric surgery. The beneficial effects of physical activity on weight loss through increased energy expenditure and appetite modulation are also firmly established. Another viable option to induce a negative energy balance, is to incorporate hypoxia per se or combine it with exercise in an individual's daily schedule. This article will present recent evidence suggesting that combining hypoxic exposure and exercise training might provide a cost-effective strategy for reducing body weight and improving cardio-metabolic health in obese individuals. The efficacy of this approach is further reinforced by epidemiological studies using large-scale databases, which evidence a negative relationship between altitude of habitation and obesity. In the United States, for instance, obesity prevalence is inversely associated with altitude of residence and urbanisation, after adjusting for temperature, diet, physical activity, smoking and demographic factors.

Derivados citotóxicos de vitanolidos isolados das folhas de Acnistus arborescens

In view of anticancer activity of 7 β-acetoxywithanolide D (2) and 7β-16α-diacetoxywithonide D (3), isolated from the leaves of Acnistus arborescens (Solanaceae), five withanolide derivatives were obtained and their structures were determined by NMR, MS and IV data analysis. The in vitro anticancer activity of these derivatives was evaluated in a panel of cancer cell lines: human breast (BC-1), human lung (Lu1), human colon (Col2) and human oral epidermoid carcinoma (KB). Compounds 2a (acetylation of 2), 3b (oxidation of 3) and 2c (hydrogenation of 2) exhibited the highest anticancer activity against human lung cancer cells, with ED50 values of 0.19, 0.25 and 0.63 μg/mL, respectively.

Amphoteric behavior of di-2-pyridyl ketone benzoylhydrazone in ethanol-water mixtures

The ligand di-2-pyridyl ketone benzoylhydrazone (DPKBH) is widely used for the determination of transition metal ions in environmental samples. Due to its low solubility in water it is used in aqueous-ethanol (1:1) solvent and for higher sensitivity the pH must be properly adjusted. The properties of DPKBH solutions must be known at different ethanol-water percentages in order to achieve higher sensitivity and/or selectivity for metal analysis. The acid-base behavior of this reagent in aqueous-ethanol solvent and the dissociation/ionization constants (pK1 and pK2) of DPKBH have been determined in different aqueous-ethanol solvent mixtures (10, 20, 30 and 50 % V/V of ethanol) from potentiometric titrations at 25.0 ± 0.1° C. As the amount of ethanol increases from 10 to 30% the pK1 and pK2 values increased, but they decreased in 50% of the organic solvent. The results are correlated with the medium composition and its effects.

Composição florística e estrutura do estrato inferior da floresta de várzea na área de proteção ambiental Ilha do Combu, município de Belém, estado do Pará

O estrato inferior é formado pela regeneração das espécies arbóreas, arbustivas, herbáceas, epífitas e lianas formando um nicho ecológico de vital importância para o estabelecimento e desenvolvimento da floresta. Com o objetivo de analisar a composição florística e a estrutura do estrato inferior da floresta de várzea na APA Ilha do Combu, Belém, Pará, foram alocadas 50 parcelas de 50 x 4 m e divididas em 25 subparcelas de 2 x 2 m. Foram identificadas e quantificadas todas as espécies com Diâmetro à Altura do Peito (DAP) d" 10 cm. Calcularam-se a diversidade, densidade e frequência relativas, categoria de tamanho relativa e regeneração natural relativa. Foram amostrados 22.221 indivíduos, 67 famílias, 153 gêneros e 223 espécies, e o índice de Shannon (H') foi de 3,72 nat/ind e a equabilidade (J'), de 0,69. Fabaceae, Malvaceae e Arecaceae destacaram-se em riqueza de espécies e Euterpe oleracea e Virola surinamensis em densidade relativa, categoria de tamanho relativa e regeneração natural relativa. O hábito arbóreo apresentou o maior número de espécies e indivíduos nas classes de tamanhos 1 e 2. Os mecanismos de adaptação e a produção de frutos estão relacionados com a diversidade da área, onde as espécies com estratégias mais eficientes são dominantes e mais representativas quantitativamente na comunidade.

Hearing Impairment and Tinnitus in the Elderly

The purpose of this study was to gather information on hearing impairment and related factors among elderly people. The HHIE-S questionnaire (Hearing Handicap Inventory for Elderly-Screening) and a single hearing question (”Do you feel you have a hearing loss”) were compared to audiometric hearing thresholds (N=164). HHIE-S was reliable for detecting moderate or worse hearing impairment. The single question was equally sensitive and more specific in identifying mild hearing impairment. The prevalence of hearing impairment was evaluated in four age cohorts (70, 75, 80 and 85 years, N=4067) in Turku, Finland. The HHIE-S cut-off score >8 as an indicator of at least mild hearing impairment yielded prevalence values of 37.7% - 54.1%, and a score >18 (moderate or more severe hearing impairment) was 21.1% - 38.9%. The single question test was positive in 25.5% - 46.2%. Hearing aid compliance and problems experienced by hearing aid users were recorded as informed by the participants in a mailed interview (N=249/4067). The hearing aids were used daily by 55.4%, and never by 10.7%. Use sank with advancing age. The disturbance caused by tinnitus among 583 subjects was compared to their level of alexithymia (TAS-20) and depressiveness (BDI). Depressiveness was weakly associated with annoying tinnitus, but not alexithymia. The prevalence of hearing impairment can be measured by enquiry. Hearing aid compliance should be improved by technical means and better counseling. The factors affecting the distress experienced by tinnitus patients need further study.

Soropositividade para brucelose em suínos em abatedouros

O presente trabalho teve por objetivo investigar a soropositividade para brucelose em suínos em abatedouros. Foram coletados 910 soros de suínos, procedentes de 30 propriedades, abatidos em frigoríficos da região central do estado de São Paulo, e submetidos às provas de soroaglutinaçao com antígeno tamponado acidificado (AAT) e 2-Mercaptoetanol (2-Me) objetivando determinar a ocorrência da enfermidade nesta espécie. Do total de soros avaliados foram observados 25 (2,7%) animais reagentes ao AAT pertencentes a 10 propriedades, caracterizando 36% de propriedades positivas. Dos animais positivos ao AAT, 16% apresentaram titulo de 25 (incompleto) e 52% titulo de 25 na soroaglutinação lenta (SAL), 8% apresentaram titulo de 50 incompleto na SAL e 25 incompleto no 2-ME e 8% apresentaram titulo de 50 na SAL e 25 no 2-ME. Estes resultados demonstram o elevado percentual de propriedades positivas para brucelose nesta região e ressaltam a necessidade de implementação de programas oficiais efetivos para o controle da brucelose suína.

Segurança das condições de aplicação de herbicidas com aerobarco em plantas daninhas aquáticas no lago da Hidrelétrica de Jupiá

Os objetivos deste trabalho foram quantificar as exposições dérmicas (EDs) e respiratórias (ERs) proporcionadas ao piloto e ao seu ajudante nas aplicações de herbicidas para o controle de plantas daninhas aquáticas com aerobarco; classificar essas condições de trabalho em seguras ou inseguras; e calcular a necessidade de controle das exposições (NCE) e o tempo de trabalho seguro (TTS). O aerobarco utilizado tinha casco de alumínio (4,85 x 2,42 m) e acionamento por hélice acoplada a motor a gasolina de 350 HP. O equipamento de pulverização era composto por bomba de diafragma com fluxo máximo de 49,69 L min-1, pressão máxima de 25 kg cm-2, acionada por motor a gasolina de 4 HP, e tanque de calda de 189 L. A barra de pulverização de alumínio era composta de duas seções laterais de 3 m, posicionadas na linha entre o encosto do banco do piloto e o início da estrutura protetora da hélice. Cada seção da barra tinha seis bicos com pontas de jato plano com indução de ar AI 100 03, espaçados de 0,5 m, e uma ponta OC 20 fixada em cada extremidade. O conjunto de pontas pulverizava faixas de 6 m de largura e aplicava o volume de calda de 200 L ha-1. O sistema tinha gerenciador de fluxo, controlado por central eletrônica acoplada a DGPS (com precisão submétrica), para corrigir automaticamente a vazão em função de alterações na velocidade real da embarcação. As EDs e ERs aos herbicidas foram calculadas com os dados substitutos das exposições às caldas, avaliadas com os traçadores cobre e manganês adicionados às caldas. As exposições foram extrapoladas para uma jornada de trabalho de seis horas. A segurança das condições de trabalho foi determinada com o cálculo da margem de segurança (MS), utilizando-se a fórmula MS = (NOEL x 70)/(QAE x 10), em que QAE = quantidade absorvível da exposição. As condições de trabalho foram classificadas em seguras, se MS>1, ou inseguras, se MS<1. As exposições proporcionadas pelas condições de trabalho foram de 10,65 mL de calda por dia para o piloto e de 16,80 mL por dia para o ajudante, que fica sentado em uma cadeira a 2,0 m à frente do piloto e da barra de pulverização. Classificaram-se como seguras as aplicações dos herbicidas glyphosate (Rodeo, 6 L ha-1), 2,4D (DMA 806 BR, 8 L ha-1) e fluridone (Sonar AQ, 0,4 L ha-1), para o piloto e o seu ajudante. Classificou-se como insegura a aplicação do herbicida diquat (Reward, 4,0 L ha-1) para as duas condições de trabalho, cujas necessidades de controle das exposições calculadas foram de 65% para o piloto e de 78% para o ajudante do piloto.

Bancos de sementes de plantas daninhas em cultivos de mandioca na Amazônia Central

Este estudo investigou a densidade de sementes e a riqueza de espécies dos bancos de sementes de plantas daninhas em cultivos de mandioca (Manihot esculenta), em pequenas propriedades rurais localizadas em Manacapuru, Amazonas. Nos cultivos foram estabelecidas quatro parcelas, de onde foram coletadas 20 amostras (0,0225 m²) de 15 x 15 cm (0,0225 m²) na camada de 0-5 cm e três amostras nas profundidades de 5-10 e 10-30 cm, totalizando 104 amostras. Para a contagem e identificação das sementes, utilizou-se a técnica de emergência de plântulas em casa de vegetação. As plântulas foram identificadas, inicialmente, por morfotipo e, quando possível, até espécie. O monitoramento foi feito durante nove meses. Houve diferença significativa na densidade de sementes (Kruskal Wallis, 5%; p<0,05) entre as parcelas e verificou-se uma média de 5.113 sementes m-2, na profundidade de 0-5 cm. Na profundidade de 5-10 cm, os cultivos de mandioca apresentaram uma média de 1.111,25 sementes m-2, enquanto na profundidade de 10-30 cm a média foi de 285 sementes m-2. Os bancos de sementes dos cultivos de mandioca foram constituídos principalmente por espécies herbáceas - características de áreas agrícolas e ambientes perturbados. A realização de uma capina anual não foi suficiente para controlar as plantas daninhas e reduzir a intensidade da interferência negativa sobre a cultura, sendo necessários maiores cuidados nos períodos que antecedem as épocas de floração e produção de sementes, de acordo com a disponibilidade de mão de obra.

Isolation of bovine plasma albumin by liquid chromatography and its polymerization for use in immunohematology

The aim of the method described here is to remove hemoglobin, the major contaminant in the bovine plasma obtained from slaughterhouses, by adding a mixture of 19% cold ethanol and 0.6% chloroform, followed by fibrinogen and globulin precipitation by the Cohn method and nonspecific hemagglutinin by thermocoagulation. The experimental volume of bovine plasma was 2,000 ml per batch. Final purification was performed by liquid chromatography using the ion-exchange gel DEAE-Sepharose FF. The bovine albumin thus obtained presented > or = 99% purity, a yield of 25.0 ± 1.2 g/l plasma and >71.5% recovery. N-acetyl-DL-tryptophan (0.04 mmol/g protein) and sodium caprylate (0.04 mmol/g protein) were used as stabilizers and the final concentration of albumin was adjusted to 22.0% (w/v), pH 7.2 to 7.3. Viral inactivation was performed by pasteurization for 10 h at 60°C. The bovine albumin for the hemagglutination tests used in immunohematology was submitted to chemical treatment with 0.06% (w/v) glutaraldehyde and 0.1% (w/v) formaldehyde at 37°C for 12 h to obtain polymerization. A change in molecular distribution was observed after this treatment, with average contents of 56.0% monomers, 23.6% dimers, 12.2% trimers and 8.2% polymers. The tests performed demonstrated that this polymerized albumin enhances the agglutination of Rho(D)-positive red cells by anti-Rho(D) serum, permitting and improving visualization of the results.

Determinants of Bone Strength and Predictors of Hip Fracture among Finnish Adults. Results from the Health 2000 Survey and the Mini-Finland Health Survey

The objective of this thesis was to identify the determinants of bone strength and predictors of hip fracture in representative samples of Finnish adults. A secondary objective was to construct a simple multifactorial model for hip fracture prediction over a 10-year follow-up period. The study was based on the Health 2000 Survey conducted during 2000 to 2001 (men and women aged 30 years or over, n=6 035) and the Mini-Finland Health Survey conducted during 1978 to 1980 (women aged 45 years or over, n=2 039). Study subjects participated in health interviews and comprehensive health examination. In the Health 2000 Survey, bone strength was assessed by means of calcaneal quantitative ultrasound (QUS). The follow-up information about hip fractures was drawn from the National Hospital Discharge Register. In this study, age, weight, height, serum 25-hydroxyvitamin D (S-25(OH)D), physical activity, smoking and alcohol consumption as well as menopause and eventual HRT in women were found to be associated with calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS). Parity was associated with a decreased risk of hip fracture in postmenopausal women. Age, height, weight or waist circumference, quantitative ultrasound index (QUI), S-25(OH)D and fall-related factors, such as maximal walking speed, Parkinson’s disease, and the number of prescribed CNS active medication were significant independent predictors of hip fracture. At the population level, the incremental value of QUS appeared to be minor in hip fracture prediction when the fall-related risk factors were taken into account. A simple multifactorial model for hip fracture prediction presented in this study was based on readily available factors (age, gender, height, waist circumference, and fallrelated factors). Prospective studies are needed to test this model in patient-based study populations.

Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling

Data about the impact of bariatric surgery (BS) and subsequent weight loss on bone are limited. The objective of the present study was to determine bone mineral density (BMD), bone remodeling metabolites and hormones that influence bone trophism in premenopausal women submitted to BS 9.8 months, on average, before the study (OGg, N = 16). The data were compared to those obtained for women of normal weight (CG, N = 11) and for obese women (OG, N = 12). Eight patients in each group were monitored for one year, with the determination of BMD, of serum calcium, phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D, insulin-like growth factor-I (IGF-I) and osteocalcin, and of urinary calcium and deoxypyridinoline. The biochemical determinations were repeated every three months in the longitudinal study and BMD was measured at the end of the study. Parathyroid hormone levels were similar in the three groups. IGF-I levels (CG = 332 ± 62 vs OG = 230 ± 37 vs OGg = 128 ± 19 ng/mL) were significantly lower in the operated patients compared to the non-operated obese women. Only OGg patients presented a significant fall in BMD of 6.2% at L1-L4, of 10.2% in the femoral neck, and of 5.1% in the forearm. These results suggest that the weight loss induced by BS is associated with a significant loss of bone mass even at sites that are not influenced by weight overload, with hormonal factors such as IGF-I being associated with this process.