The emergence of YMDD mutants precedes biochemical flare by 19 weeks in lamivudine-treated chronic hepatitis B patients: an opportunity for therapy reevaluation

Given the loss of therapeutic efficacy associated with the development of resistance to lamivudine (LMV) and the availability of new alternative treatments for chronic hepatitis B patients, early detection of viral genotypic resistance could allow the clinician to consider therapy modification before viral breakthrough and biochemical relapse occur. To this end, 28 LMV-treated patients (44 ± 12 years; 24 men), on their first therapy schedule, were monitored monthly at four Brazilian centers for the emergence of drug resistance using the reverse hybridization-based INNO-LiPA HBV DR assay and occasionally sequencing (two cases). Positive viral responses (HBV DNA clearance) after 6, 12, and 18 months of therapy were achieved by 57, 68, and 53% of patients, while biochemical responses (serum alanine aminotransferase normalization) were observed in 82, 82, and 53% of cases. All viral breakthrough cases (N = 8) were related to the emergence of YMDD variants observed in 7, 21, and 35% of patients at 6, 12, and 18 months, respectively. The emergence of these variants was not associated with viral genotype, HBeAg expression status, or pretreatment serum alanine aminotransferase levels. The detection of resistance-associated mutations was observed before the corresponding biochemical flare (41 ± 14 and 60 ± 15 weeks) in the same individuals. Then, if highly sensitive LMV drug resistance testing is carried out at frequent and regular intervals, the relatively long period (19 ± 2 weeks) between the emergence of viral resistance and the onset of biochemical relapse can provide clinicians with ample time to re-evaluate drug therapy.

The effect of a low dose of clenbuterol on rat soleus muscle submitted to joint immobilization

The aim of the present study was to evaluate the effect of joint immobilization on morphometric parameters and glycogen content of soleus muscle treated with clenbuterol. Male Wistar (3-4 months old) rats were divided into 4 groups (N = 6 for each group): control, clenbuterol, immobilized, and immobilized treated with clenbuterol. Immobilization was performed with acrylic resin orthoses and 10 µg/kg body weight clenbuterol was administered subcutaneously for 7 days. The following parameters were measured the next day on soleus muscle: weight, glycogen content, cross-sectional area, and connective tissue content. The clenbuterol group showed an increase in glycogen (81.6%, 0.38 ± 0.09 vs 0.69 ± 0.06 mg/100 g; P < 0.05) without alteration in weight, cross-sectional area or connective tissue compared with the control group. The immobilized group showed a reduction in muscle weight (34.2%, 123.5 ± 5.3 vs 81.3 ± 4.6 mg; P < 0.05), glycogen content (31.6%, 0.38 ± 0.09 vs 0.26 ± 0.05 mg/100 mg; P < 0.05) and cross-sectional area (44.1%, 2574.9 ± 560.2 vs 1438.1 ± 352.2 µm²; P < 0.05) and an increase in connective tissue (216.5%, 8.82 ± 3.55 vs 27.92 ± 5.36%; P < 0.05). However, the immobilized + clenbuterol group showed an increase in weight (15.9%; 81.3 ± 4.6 vs 94.2 ± 4.3 mg; P < 0.05), glycogen content (92.3%, 0.26 ± 0.05 vs 0.50 ± 0.17 mg/100 mg; P < 0.05), and cross-sectional area (19.9%, 1438.1 ± 352.2 vs 1724.8 ± 365.5 µm²; P < 0.05) and a reduction in connective tissue (52.2%, 27.92 ± 5.36 vs 13.34 ± 6.86%; P < 0.05). Statistical analysis was performed using Kolmogorov-Smirnov and homoscedasticity tests. For the muscle weight and muscle glycogen content, two-way ANOVA and the Tukey test were used. For the cross-sectional area and connective tissue content, Kruskal-Wallis and Tukey tests were used. This study emphasizes the importance of anabolic pharmacological protection during immobilization to minimize skeletal muscle alterations resulting from disuse.

Effect of frequency of static stretching on flexibility, hamstring tightness and electromyographic activity

We compared the effect of the number of weekly repetitions of a static stretching program on the flexibility, hamstring tightness and electromyographic activity of the hamstring and of the triceps surae muscles. Thirty-one healthy subjects with hamstring tightness, defined as the inability to perform total knee extension, and shortened triceps surae, defined by a tibiotarsal angle wider than 90° during trunk flexion, were divided into three groups: G1 performed the stretching exercises once a week; G2, three times a week, and G3, five times a week. The parameters were determined before and after the stretching program. Flexibility improved in all groups after intervention, from 7.65 ± 10.38 to 3.67 ± 12.08 in G1, from 10.73 ± 12.07 to 0.77 ± 10.45 in G2, and from 14.20 ± 10.75 to 6.85 ± 12.19 cm in G3 (P < 0.05 for all comparisons). The increase in flexibility was higher in G2 than in G1 (P = 0.018), while G2 and G3 showed no significant difference (G1: 4 ± 2.17, G2: 10 ± 5.27; G3: 7.5 ± 4.77 cm). Hamstring tightness improved in all groups, from 37.90 ± 6.44 to 29 ± 11.65 in G1, from 39.82 ± 9.63 to 21.91 ± 8.40 in G2, and from 37.20 ± 6.63 to 26.10 ± 5.72° in G3 (P < 0.05 for all comparisons). During stretching, a statistically significant difference was observed in electromyographic activity of biceps femoris muscle between G1 and G3 (P = 0.048) and G2 and G3 (P = 0.0009). No significant differences were found in electromyographic activity during maximal isometric contraction. Stretching exercises performed three times a week were sufficient to improve flexibility and range of motion compared to subjects exercising once a week, with results similar to those of subjects who exercised five times a week.

Anthropometric midarm measurements can detect systemic fat-free mass depletion in patients with chronic obstructive pulmonary disease

Our objective was to determine whether anthropometric measurements of the midarm (MA) could identify subjects with whole body fat-free mass (FFM) depletion. Fifty-five patients (31% females; age: 64.6 ± 9.3 years) with mild/very severe chronic obstructive pulmonary disease (COPD), 18 smokers without COPD (39% females; age: 49.0 ± 7.3 years) and 23 never smoked controls (57% females; age: 48.2 ± 9.6 years) were evaluated. Spirometry, muscle strength and MA circumference were measured. MA muscle area was estimated by anthropometry and MA cross-sectional area by computerized tomography (CT) scan. Bioelectrical impedance was used as the reference method for FFM. MA circumference and MA muscle area correlated with FFM and biceps and triceps strength. Receiver operating characteristic curve analysis showed that MA circumference and MA muscle area cut-off points presented sensitivity and specificity >82% to discriminate FFM-depleted subjects. CT scan measurements did not provide improved sensitivity or specificity. For all groups, there was no significant statistical difference between MA muscle area [35.2 (29.3-45.0) cm²] and MA cross-sectional area values [36.4 (28.5-43.3) cm²] and the linear correlation coefficient between tests was r = 0.77 (P < 0.001). However, Bland-Altman plots revealed wide 95% limits of agreement (-14.7 to 15.0 cm²) between anthropometric and CT scan measurements. Anthropometric MA measurements may provide useful information for identifying subjects with whole body FFM depletion. This is a low-cost technique and can be used in a wider patient population to identify those likely to benefit from a complete body composition evaluation.

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9% and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15%), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3% and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3%) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.

Identification of microRNAs and mRNAs associated with multidrug resistance of human laryngeal cancer Hep-2 cells

Multidrug resistance (MDR) poses a serious impediment to the success of chemotherapy for laryngeal cancer. To identify microRNAs and mRNAs associated with MDR of human laryngeal cancer Hep-2 cells, we developed a multidrug-resistant human laryngeal cancer subline, designated Hep-2/v, by exposing Hep-2 cells to stepwise increasing concentrations of vincristine (0.02-0.96'µM). Microarray assays were performed to compare the microRNA and mRNA expression profiles of Hep-2 and Hep-2/v cells. Compared to Hep-2 cells, Hep-2/v cells were more resistant to chemotherapy drugs (∼45-fold more resistant to vincristine, 5.1-fold more resistant to cisplatin, and 5.6-fold more resistant to 5-fluorouracil) and had a longer doubling time (42.33±1.76 vs 28.75±1.12'h, P<0.05), higher percentage of cells in G0/G1 phase (80.98±0.52 vs69.14±0.89, P<0.05), increased efflux of rhodamine 123 (95.97±0.56 vs 12.40±0.44%, P<0.01), and up-regulated MDR1 expression. A total of 7 microRNAs and 605 mRNAs were differentially expressed between the two cell types. Of the differentially expressed mRNAs identified, regulator of G-protein signaling 10, high-temperature requirement protein A1, and nuclear protein 1 were found to be the putative targets of the differentially expressed microRNAs identified. These findings may open a new avenue for clarifying the mechanisms responsible for MDR in laryngeal cancer.

The efficacy of moxifloxacin-based triple therapy in treatment of Helicobacter pylori infection: a systematic review and meta-analysis of randomized clinical trials

Recent evidence shows that moxifloxacin could exert an antimicrobial effect against Helicobacter pylori in both in vitroand in vivo models. To systematically evaluate whether moxifloxacin-containing triple therapy could improve eradication rates and reduce side effects in first-line or second-line anti-H. pyloritreatment, eligible articles were identified by searches of electronic databases. We included all randomized trials comparing moxifloxacin-based triple therapy with standard triple or quadruple therapy during H. pylori eradication treatment. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/sensitivity analysis was also performed. We identified seven randomized trials (n=1263). Pooled H. pylori eradication rates were 79.03% (95%CI: 75.73-82.07) and 68.33% (95%CI: 64.44-72.04) for patients with moxifloxacin-based triple therapy or with standard triple or quadruple therapy, respectively (intention-to-treat analysis). The odds ratio (OR) was 1.82 (95%CI: 1.17-2.81), the occurrence of total side effects was 15.23% (95%CI: 12.58-18.20) and 27.17% (95%CI: 23.64-30.92) for groups with or without moxifloxacin, and the summary OR was 0.45 (95%CI: 0.26-0.77). In subgroup analyses, we noted that the second-line eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (73.33 vs 60.17%, OR: 1.78, 95%CI: 1.16-2.73, P<0.001). However, there was no difference in first-line eradication treatment. Findings from this meta-analysis suggest that moxifloxacin-based triple therapy is more effective and better tolerated than standard triple or quadruple therapy. Therefore, a moxifloxacin-based triple regimen should be used in the second-line treatment of H. pylori infection.

Determinação de minerais em café cru

Dois métodos de preparo de amostra foram avaliados: via seca e via úmida, para a determinação e quantificação dos minerais Al, Ba, Ca, Co, Cu, Fe, K, Mg, Mn, Ni, P e Zn em café cru, empregando-se a técnica de Espectrometria de Emissão Ótica em Plasma Indutivamente Acoplado (ICP-OES). As concentrações dos minerais não diferiram significativamente ao nível de 5% (Teste F) entre os dois métodos empregados. Para avaliar a exatidão dos métodos testados foi realizada a recuperação dos minerais em uma amostra de café. Os resultados obtidos pelos métodos empregando via seca e via úmida foram, respectivamente: Al = 93% e 104%; Ba = 85% e 54%; Ca = 99% e 108%; Co = 98% e 96%; Cu = 78% e 96%; Fe = 96% e 96%; K = 91% e 82%; Mg = 100% e 95%; Mn = 104% e 101%; Ni = 95% e 107%; P = 101% e 104%; Zn = 89% e 96%. O método por via seca foi empregado para a determinação dos teores de minerais em 45 amostras de café provenientes de diferentes regiões de cultivo dos Estados de São Paulo, Minas Gerais e Bahia. Os teores de minerais (em mg kg-1) encontrados nas diferentes amostras variaram entre: Al (0,612 a 32,2), Ba (1,11 a 17,6), Ca (925 a 1889), Co (0 a 1,16), Cu (6,21 a 369), Fe (23,3 a 367), K (12252 a 17205), Mg (1526 a 2059), Mn (14,2 a 60,4), Ni (0 a 44,2), P (1172 a 1826) e Zn (3,71 a 57,0). O emprego da técnica instrumental de ICP-OES e digestão da amostra por via seca mostraram-se adequados para a determinação simultânea de elementos minerais em café, uma vez que os níveis de precisão e exatidão obtidos foram satisfatórios.

Propriedades físicas e químicas de feijão comum preto, cultivar Iapar 44, após envelhecimento acelerado

Feijão armazenado por período longo em temperatura e umidade relativa elevadas torna-se endurecido e resistente ao cozimento devido ao desenvolvimento do defeito "difícil de cozinhar". Este trabalho teve como objetivo avaliar algumas propriedades físicas e químicas de feijão comum preto (Phaseolus vulgaris L.) cultivar Iapar 44, envelhecido. O envelhecimento do feijão foi acelerado a 41ºC e 75% de UR, por 30 e 60 dias, e feijão novo mantido a 5ºC e 60% de UR foi considerado controle. Foram avaliados o tempo de cozimento, por meio do equipamento de Mattson adaptado; a composição química e o pH dos grãos; a solubilidade em água e o perfil eletroforético das proteínas. Os resultados foram submetidos à análise de variância e teste de comparação de médias de Tukey (p<0,05). Verificou-se que o armazenamento, nos dois tempos, causou: aumento no tempo de cozimento dos grãos; diminuição do teor de umidade, aumento do teor de cinzas e manutenção dos teores de proteínas, lipídeos e carboidratos; diminuição do pH e diminuição da solubilidade e a mudança do perfil eletroforético das proteínas. Estes resultados estão de acordo com dados da literatura, que demonstram que durante o armazenamento de feijão em alta temperatura e umidade relativa há formação de ácidos, conduzindo à diminuição da solubilidade e estabilidade térmica das proteínas.

Rendimentos do abate e composição da carne de ema (Rhea americana)

O objetivo deste trabalho foi estudar o desempenho zootécnico da ema (Rhea americana), rendimentos do abate, composição química e análise sensorial da carne. Onze animais foram submetidos a um sistema de confinamento, recebendo ração balanceada à vontade e com acesso a um piquete. Antes do abate as emas permaneceram em jejum hídrico por 12 h, foram pesadas e submetidas ao processamento: insensibilização, sangria, depenagem manual, esfola e evisceração. As emas apresentaram peso vivo médio, no momento do abate, de 19,393 kg, desempenho médio de 529,82 de consumo de ração/dia, 53,20 g de ganho de peso/dia e 9,44 de conversão alimentar. Em relação ao peso de carcaça, mostraram rendimento médio de 63,33% de carne, 5,09% de gordura e 22% de ossos. A composição centesimal média da carne de ema foi de 22,81% de proteína, 1,59% de lipídios, 1,62% de cinzas e de 74,72% de umidade. O conteúdo de colágeno variou de 0,94% a 1,12% e o teor de colesterol foi de 65,44 mg por 100 g de carne. Pela análise sensorial, verificou-se que a carne de ema processada foi bem aceita pelos provadores. Assim, admite-se que a carne de ema pode ser consumida como fonte de proteína animal com baixo teor de lipídios.

Caracterização de concentrado proteico de feijão comum preto, cultivar Iapar 44, novo e envelhecido

Feijões endurecidos devido a condições impróprias de armazenamento têm sua qualidade e aceitabilidade afetadas. Para que sejam utilizados como produtos comestíveis, é necessário o estudo de processos tecnológicos que possibilitem seu aproveitamento. Portanto, este trabalho teve como objetivo caracterizar concentrados proteicos obtidos de feijão comum preto (Phaseolus vulgaris L.), cultivar Iapar 44, novo e envelhecido, bem como avaliar suas propriedades funcionais e sua utilização como ingrediente alimentar. O envelhecimento do feijão foi acelerado a 41 °C e 75% UR, por 30 e 60 dias, o feijão novo armazenado a 5 °C foi utilizado como controle. Concentrados proteicos foram obtidos por extração alcalina com NaOH 0,02% e posterior precipitação isoelétrica com HCl concentrado. Avaliaram-se o rendimento, composição química, perfil eletroforético das proteínas e propriedades funcionais de: solubilidade, absorção de água, formação de gel, absorção de óleo, capacidade e atividade emulsificante, estabilidade da emulsão, formação e estabilidade da espuma dos concentrados. O rendimento dos concentrados foi de 15% e estes apresentaram 75% de proteínas com perfil eletroforético e solubilidade proteica em água que variaram com o tempo de armazenamento. A solubilidade foi menor nos pHs 4 e 5. A absorção de água e a capacidade de formação de gel aumentaram com o armazenamento do feijão. A atividade emulsificante e estabilidade da emulsão foram prejudicadas pelo armazenamento de 60 dias. As demais propriedades não foram alteradas pelo armazenamento. Os resultados indicam possibilidades de uso do concentrado proteico de feijão armazenado como ingrediente alimentar.

Influence of temperature on the respiration rate of minimally processed organic carrots (Daucus Carota L. cv. Brasília)

The objective of this work was to study the influence of temperature on the respiration rate of minimally processed organic carrots (Daucus Carota L. cv. Brasília) with and without the application of a gelatin film. The samples were packed in flexible bags and stored at 1, 5 and 10 °C. During the five days of storage, the CO2 and O2 concentrations in the headspace of the package were monitored by gas chromatography, and the mathematical model based on enzymatic kinetics was used to estimate the respiration rate of minimally processed organic carrots. The effect of temperature on the respiration rate was evaluated by the Arrhenius equation. The results showed that the O2 concentration decreased during the storage period and the CO2 concentration increased. The lowest O2 concentrations of 2.59 and 2.66% were found for the samples stored at 10 °C with and without the film, respectively. For the CO2 concentration, the highest concentrations of 16.25 and 16.32% were again found for the temperature of 10 °C with and without the application of the film, respectively. At the temperature of 1 °C, the maximum respiratory rates for the samples without and with the film were 10.82 and 10.44 mL CO2.kg-1/hour, respectively, after 72 hours of storage. The greatest respiratory rate was obtained at 10 °C, the maximum peak being reached after 50 hours. Activation energy values were of 50.59 kJ.mol-1, for the samples with the film, and 51.88 kJ.mol-1 for the samples without the film.

Density and rheological parameters of goat milk

The rheological behavior and density of goat milk was studied as a function of solids concentration (10.5 to 50.0%) and temperature (273 to 331 k). Newtonian behavior was observed for values of total solids (TS) between 10.5 and 22.0% and temperatures from 276 to 331 k changing to pseudoplastic behavior without yield stress for TS from 25.0 to 39.4% at the same range of temperature. Goat milk with TS between 44.3 to 50.0% and temperatures of 273 to 296 k showed yield stress in addition to pseudoplastic behavior. At 303 to 331 k the power law model was observed again, without yield stress. The density of goat milk ranged from 991.7 to 1232.4 kg.m-3.