Cellular dynamics as a marker of normal-to-cancer transition in human cells.

Normal-to-cancer (NTC) transition is known to be closely associated to cell´s biomechanical properties which are dependent on the dynamics of the intracellular medium. This study probes different human cancer cells (breast, prostate and lung), concomitantly to their healthy counterparts, aiming at characterising the dynamical profile of water in distinct cellular locations, for each type of cell, and how it changes between normal and cancer states. An increased plasticity of the cytomatrix is observed upon normal-to-malignant transformation, the lung carcinoma cells displaying the highest flexibility followed by prostate and breast cancers. Also, lung cells show a distinct behaviour relative to breast and prostate, with a higher influence from hydration water motions and localised fast rotations upon NTC transformation. Quasielastic neutron scattering techniques allowed to accurately distinguish the different dynamical processes taking place within these highly heterogeneous cellular systems. The results thus obtained suggest that intracellular water dynamics may be regarded as a specific reporter of the cellular conditions-either healthy or malignant.

Water dynamics in human cancer and non-cancer tissues.

Normal-to-malignant transformation is a poorly understood process associated with cellular biomechanical properties. These are strongly dependent on the dynamical behaviour of water, known to play a fundamental role in normal cellular activity and in the maintenance of the three-dimensional architecture of the tissue and the functional state of biopolymers. In this study, quasi-elastic neutron scattering was used to probe the dynamical behaviour of water in human cancer specimens and their respective surrounding normal tissue from breast and tongue, as an innovative approach for identifying particular features of malignancy. This methodology has been successfully used by the authors in human cells and was the first study of human tissues by neutron scattering techniques. A larger flexibility was observed for breast versus tongue tissues. Additionally, different dynamics were found for malignant and non-malignant specimens, depending on the tissue: higher plasticity for breast invasive cancer versus the normal, and an opposite effect for tongue. The data were interpreted in the light of two different water populations within the samples: one displaying bulk-like dynamics (extracellular and intracellular/cytoplasmic) and another with constrained flexibility (extracellular/interstitial and intracellular/hydration layers).

Eustigmatophyte strains with potential interest in cancer prevention and treatment: partial chemical characterization and evaluation of cytotoxic and antioxidant activity.

The interest in bioactive compounds from microalgae is increasing since they have medicinal and nutritional areas. The present work aims to evaluate the potential pharmaceutical interest of extracts from three eustigmatophyte strains from the Coimbra Collection of Algae (ACOI): Chlorobotrys gloeothece, Chlorobotrys regularis and Characiopsis aquilonaris. Antioxidant and antiproliferative activities were determined as well as chlorophyll a, carotenoid and phenolic total contents. In addition, major pigments and sterols were identified and quantified. The three strains were grown until the stationary phase and then the biomass was extracted. Antioxidant activity was measured by TEAC, DPPH and FRAP assays and antiproliferative effect was assessed by the MTT method on MCF-7, PC-3 and NHDF cells. The pigment and phenolic total contents were determined by spectrophotometry. Of these strains, C. aquilonaris showed the highest antioxidant activity measured by TEAC and FRAP assays (23.98 ± 0.01 µmol TE eq g-1 DW and 42.57 ± 0.04 µmol TE eq g-1 DW, respectively), a selective effect in reduting MCF-7 cells proliferation and a larger amount of chlorophyll a, carotenoids and phenolic content (18.40 ± 0.00 µg chlorophyll a mg-1 DW, 2.27 ± 0.00 mg carotenoids g-1 DW and 6.23 ± 0.01 mg GAE g-1 DW, respectively). A positive correlation between chlorophyll a and TEAC assay was observed, as well as between carotenoids and TEAC and FRAP assays, suggesting these compounds as important contributors to significant antioxidant activity. Violaxanthin, cholesterol and stigmasterol were present in larger amount in C. aquilonaris while C. regularis showed a higher amount of ß-carotene. These results suggest that these three ACOI eustigmatophytes are promising for applications in the improvement of human health, particularly in cancer prevention and treatment.

Short implants versus bone augmentation in combination with standard-length implants in posterior atrophic partially edentulous mandibles: systematic review and meta-analysis with the Bayesian approach.

The use of short implants as an alternative to bone reconstruction techniques for the placement of standard-length dental implants is a debated topic. The aim of this study was to perform a systematic review and meta-analysis in order to assist in the clinical decision making about the most appropriate approach for the fixed rehabilitation of the posterior atrophic partially edentulous lower jaws. Only randomized trials with at least 1-year follow-up were included. Of the 1024 studies initially retrieved, 14 articles were selected and independently evaluated by two reviewers. Finally, four studies were included, and underwent data extraction and meta-analysis with the Bayesian approach. Both treatment approaches provide high implant survival rate after 1year of function. However, the probability of survival rate of short implants being greater than standard length implants is 84%, and the probability of complications using short implants being greater than standard-length implants is 15.7%. In spite of similar survival rates when the residual bone is sufficient for placement of short implants, the latter should be preferred to augmentation techniques and standard-length implants due to fewer complications, lower morbidity and greater comfort for patients.

Does Clinical Treatment with Phenylbutazone and Meloxicam in the Pre-ovulatory Period Influence the Ovulation Rate in Mares?

The presence of anovulatory haemorrhagic follicles during the oestrous cycle of mares causes financial impacts, slowing conception and increasing the number of services per pregnancy. Non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and phenylbutazone are used in the treatment of several disorders in mares, and these drugs can impair the formation of prostaglandins (PGs) and consequently interfere with reproductive activity. This study aimed to evaluate the effects of treatment with NSAIDs on the development of pre-ovulatory follicles in mares. In total, 11 mares were studied over three consecutive oestrous cycles, and gynaecological and ultrasound examinations were performed every 12 h. When 32-mm-diameter follicles were detected, 1 mg of deslorelin was administered to induce ovulation. The first cycle was used as a control, and the mares received only a dose of deslorelin. In the subsequent cycles, in addition to receiving the same dose of deslorelin, each mare was treated with NSAIDs. In the second cycle, 4.4 mg/kg of phenylbutazone was administered, and in the third cycle, 0.6 mg/kg of meloxicam was administered once a day until ovulation or the beginning of follicular haemorrhage. All of the mares ovulated between 36 and 48 h after the induction in the control cycle. In the meloxicam cycle, 10 mares (92%) did not ovulate, while in the phenylbutazone cycle, nine mares (83%) did not ovulate. In both treatments, intrafollicular hyperechoic spots indicative of haemorrhagic follicles were observed on ultrasound. Thus, our results suggested that treatment with meloxicam and phenylbutazone at therapeutic doses induced intrafollicular haemorrhage and luteinization of anovulatory follicles.

Toll-like receptor 4 inhibition reduces vascular inflammation in spontaneously hypertensive rats.

AIMS: Hypertension is associated with increased levels of circulating cytokines and recent studies have shown that innate immunity contributes to hypertension. The mechanisms which hypertension stimulates immune response remain unclear, but may involve formation of neo-antigens that activate the immune system. Toll like receptor 4 (TLR4) is an innate immune receptor that binds a wide spectrum of exogenous (lipopolysaccharide) and endogenous ligands. TLR4 signaling leads to activation of nuclear factor kappa B (NFκB) and transcription of genes involved in inflammatory response. We previously demonstrated that TLR4 blockade reduces blood pressure and the augmented vascular contractility in spontaneously hypertensive rats (SHR). Here we hypothesized that inhibition of TLR4 ameliorates the vascular inflammatory process by a NFκB signaling pathway. MAIN METHODS: SHR and Wistar rats were treated with anti-TLR4 antibody (1µg/day) or unspecific IgG for 15days (i.p.). KEY FINDINGS: Anti-TLR4 treatment decreased production of reactive oxygen species and expression of IL-6 cytokine in mesenteric resistance arteries from SHR, when compared with IgG-treated SHR. Anti-TLR4 treatment also abolished the increased vascular reactivity to noradrenaline observed in IgG-treated SHR, as described before, and inhibition of NFκB decreased noradrenaline responses only in IgG-treated SHR. Mesenteric arteries from SHR treated with anti-TLR4 displayed decreased expression of MyD88, but not TRIF, key molecules in TLR4 signaling. Phosphorylation of p38 and NF-κB p65 were decreased in arteries from anti-TLR4-treated SHR versus IgG-treated SHR. SIGNIFICANCE: Together, these results suggest that TLR4 is a key player in hypertension and vascular inflammatory process by a NFκB signaling pathway.

Comparison of maximal lactate steady state with V2, V4, individual anaerobic threshold and lactate minimum speed in horses / Comparação da máxima fase estável do lactato com a V2, V4, o limiar anaeróbio individual e lactato mínimo em equinos

The anaerobic threshold is a physiologic event studied in various species. There are various methods for its assessment, recognized in the human and equine exercise physiology literature, several of these involving the relationship between blood lactate concentration (LAC) and exercise load, measured in a standardized exercise test. The aim of this study was to compare four of these methods: V2, V4, individual anaerobic threshold (IAT) and lactate minimum speed (LMS) with the method recognized as the gold standard for the assessment of anaerobic threshold, maximal lactate steady-state (MLSS). The five tests were carried out in thirteen trained Arabian horses, in which velocities and associated LAC could be measured. The mean velocities and the LAC associated with the anaerobic threshold for the five methods were respectively: V2 = 9.67±0.54; V4 = 10.98±0.47; V IAT = 9.81±0.72; V LMS = 7.50±0.57 and V MLSS = 6.14±0.45m.s-1 and LAC IAT = 2.17±0.93; LAC LMS = 1.17±0.62 and LAC MLSS = 0.84±0.21mmol.L-1. None of the velocities were statistically equivalent to V MLSS (P<0.05). V2, V4 and V LMS showed a good correlation with V MLSS , respectively: r = 0.74; r = 0.78 and r = 0.83, and V IAT did not significantly correlate with V MLSS. Concordance between the protocols was relatively poor, i.e., 3.28±1.00, 4.84±0.30 and 1.43±0.32m.s-1 in terms of bias and 95% agreement limits for V2, V4 and LMS methods when compared to MLSS. Only LAC LMS did not differ statistically from LAC MLSS. Various authors have reported the possibility of the assessment of anaerobic threshold using rapid protocols such as V4 and LMS for humans and horses. This study corroborates the use of these tests, but reveals that adjustments in the protocols are necessary to obtain a better concordance between the tests and the MLSS.

O limiar anaeróbio é um evento fisiológico estudado em várias espécies. Sua mensuração possui vários métodos reconhecidos na literatura da fisiologia do exercício humano e equino, muitos deles envolvendo a relação entre a concentração sanguínea de lactato (LAC) e a carga de exercício. O objetivo do presente estudo foi comparar quatro desses métodos: V2 , V4 , limiar anaeróbio individual (LAI) e o teste do lactato mínino (LM) com o método reconhecido na literatura como o padrão ouro para a mensuração do limiar anaeróbio, a máxima fase estável do lactato (MFEL). Os cinco testes foram realizados em treze equinos árabes treinados, nos quais as velocidades e suas respectivas LAC puderam ser quantificadas. As velocidades médias e LAC associadas ao limiar anaeróbio aferido pelos cinco métodos foram respectivamente: V2 = 9,67±0,54; V4 = 10,98±0,47; V LAI = 9.81±0.72; V LM = 7,50±0,57 e V MFEL = 6,14±0,45m.s-1 ; e LAC LAI = 2,17±0,93; LAC LM = 1,17±0,62 e LAC MFEL = 0,84±0,21mmol.L-1. Nenhuma dessas velocidades foi estatisticamente igual à V MFEL (P<0,05). A V2 , a V4 e a V LM mostraram uma boa correlação com a V MFEL , respectivamente r = 0,74; r = 0,78 e r = 0,83, e a V LAI não se correlacionou significativamente com a V MFEL. A concordância entre os protocolos foi relativamente fraca, sendo 3,28±1,00; 4,84±0,30 e 1,43±0,32m.s-1 em termos de viés e limites de concordância a 95% para os métodos V2 , V4 e LM comparados à MFEL. Muitos autores relataram a possibilidade da mensuração do limiar anaeróbio pelo uso de protocolos rápidos, como a V4 e o LM, para humanos e equinos. O presente estudo corrobora a utilização desses testes, mas revela que ajustes nos protocolos são necessários para se obter uma melhor concordância entre os mesmos e a MFEL.

Associação fitoterápica no tratamento de feridas cutâneas induzidas em equinos / Herbal combination in the treatment of equine skin induced wounds

Estudou-se a eficácia do uso tópico de um produto comercial constituído por uma associação fitoterápica como promotor da cicatrização de feridas induzidas em equinos. Uma lesão cutânea em forma de quadrado, com 5cm de lado, foi produzida cirurgicamente em ambos os lados da região glútea de oito cavalos adultos. Aleatoriamente um dos lados foi escolhido como tratado, permanecendo o contralateral como controle. As lesões do lado controle foram lavadas com água e detergente neutro e, no lado tratado, foi realizado o mesmo procedimento, seguido de aplicação tópica da associação fitoterápica. As evoluções macroscópica e microscópica do processo cicatricial foram avaliadas, e a área de cada ferida determinada no decorrer do período experimental. Foram encontradas diferenças significativas entre os lados em relação aos valores de área das feridas. Na última avaliação, o lado controle apresentou valor médio de área de 0,70cm², e o lado tratado de 1,23cm². A contração cicatricial observada em 77 dias de evolução cicatricial foi de 97,57% para o lado controle e de 95,59% para o lado tratado.

The efficiency of the topical use of a commercial product constituted by a herbal combination on the healing evolution of equine induced wounds was studied. A skin lesion in the shape of a square with 5cm sides was surgically produced on both sides of the buttocks of eight adult horses. One side was considered control and another one treated. Both control and treated sides were rinsed with water and neutral soap. Additionally, the wound on the treated side received the topical treatment with the herbal combination. Macroscopic and microscopic healing evolution of the wounds was evaluated and their areas were determined during the experimental period. There was statistical difference between wound areas. At the last evaluation, the average area of the control side was 0.70cm² and of the treated side was 1.23cm². The contraction of scar observed at 77 days was 97.57% for the control side and 95.59% for the treated side.

Parâmetros hematológicos de jumentas gestantes em diferentes períodos / Hematological parameters of pregnant donkeys in different periods

The hematological parameters and total protein concentration in healthy donkeys during pregnancy, under grass handling conditions in tropical weather, were evaluated. Fifth-two Marchador Brasileiro breed healthy donkeys, ranging from 8 to 16 years old, were evaluated, 36 of which were pregnant. The animals were separated in four groups: non pregnant (control), pregnancy from 25 to 110 days (first phase), from 111 to 210 days (second phase), and from 211 to 340 days (third phase). Total protein, erythrocyte, and leukocytes counts; packed cell volume; hemoglobin concentration; hematimetric absolute rates of mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); and mean corpuscular hemoglobin concentration (MCHC) were evaluated. Total protein and eosinophils count decreased in the first phase. Red blood cells, hemoglobin concentration, and MCHC increased in the third phase of pregnancy. However, MCV and MCH decreased in the same phase.

Determinação de eletrólitos, gases sanguíneos, osmolalidade, hematócrito, hemoglobina, base titulável e anion gap no sangue venoso de equinos destreinados submetidos a exercício máximo e submáximo em esteira rolante / Determination of electrolytes, hemogasometry, osmalility, hematocrit, hemoglobin, base concentration, and anion gap in detrained equines submitted a maximum and submaximum exercise on treadmill

Estudaram-se as alterações nos eletrólitos, nos gases sanguíneos, na osmolalidade, no hematócrito, na hemoglobina, nas bases tituláveis e no anion gap no sangue venoso de 11 equinos da raça Puro Sangue Árabe, destreinados, submetidos a exercício máximo e submáximo em esteira rolante. Esses animais passaram por período de três dias de adaptação à esteira rolante e posteriormente realizaram dois exercícios testes, um de curta e outro de longa duração. Foram coletadas amostras de sangue venoso antes, imediatamente após e 30 minutos após o término dos exercícios. Após a realização do exercício máximo, observou-se diminuição significativa no pHv, na PvCO2, no HCO3, na cBase além de elevação no AG. Detectou-se também aumento do K+, do Ht e da Hb. Ao final do exercício submáximo, constatou-se somente aumento significativo no pHv, na cBase, na SatvO2 e na PvO2. Conclui-se que os equinos submetidos a exercício máximo desenvolveram acidose metabólica e alcalose respiratória compensatória, hipercalemia e aumento nos valores de hematócrito e hemoglobina. No exercício submáximo, os animais apresentaram alcalose metabólica hipoclorêmica e não ocorreram alterações no equilíbrio hidroeletrolítico.

Changes in electrolytes, blood gas, osmolality, hematocrit, hemoglobin, base concentration, and anion gap in 11 detrained Arabian horses during exercise on a high-speed treadmill were investigated. After a period of three days of adaptation on the rolling mat, the animals were submitted to two exercises: one of short (maximum) and other of long duration (submaximum). Venous blood samples were obtained right before, and 30 minutes after the exercise. After the maximum exercise, it was observed a significative decrease in pHv, PvCO2, HCO3, and cBase and an increase in AG. It was also observed hypercalemia and increase in Ht and Hb. At the final of the submaximum exercise, it was observed significative increase in pH, cBase, SatvO2, and PvO2. So, maximum exercises can lead equines to present metabolic acidosis with respiratory alkalosis as response, hypercalemia and increase in hematocrit and hemoglobin, values. Submaximum exercises can present hypochloremic metabolic alkalosis but no alterations in the hydroelectrolitic balance.

Uso tópico de ketanserina na cicatrização de feridas cutâneas induzidas em equinos / Topical use of kentaserin on healing of experimentally-induced skin wounds in horses

Estudou-se a eficácia do uso tópico de ketanserina como promotor da cicatrização de feridas cutâneas induzidas em equinos. As feridas foram produzidas em ambos os metâmeros na região da garupa de oito cavalos adultos, em formato quadrangular, medindo cinco centímetros de lado. Aleatoriamente um dos metâmeros foi escolhido como tratado, permanecendo o contralateral como controle. As lesões do grupocontrole foram lavadas somente com água e detergente neutro e no grupo tratado foi realizado o mesmo procedimento seguido de aplicação tópica de ketanserina. A evolução macroscópica e microscópica do processo cicatricial foi avaliada e a área de cada ferida determinada no decorrer do período experimental. Não foram verificadas diferenças significativas entre as feridas do grupo-controle e do grupo tratado com ketanserina durante 56 dias de avaliação.

The efficiency of topical use of kentaserin on healing evolution of induced skin wounds in horses was studied. The experimental surgical wounds were made in both sides of the croup of eight adult horses. The wounds were square-shaped measuring 5cm of each side. One side was considered control and the opposite one treated. Both control and treated animals were rinsed with water and neutral soap. Additionally, the wound on the treated horses received the topical treatment with ketanserin. Macroscopic and microscopic healing evolution of the wounds was evaluated and their areas were determined during the experimental period. The use of topical ketanserin showed no difference between the control and the treated wounds during a period of 56 days.

Composição de fibras musculares esqueléticas de eqüinos jovens da raça Brasileiro de Hipismo / Composition of skeletal muscle fibers of young Brasileiro de Hipismo horse breed

The aim of this study was to typify the skeletal striated fibers of the gluteus medius muscle of young Brasileiro de Hipismo (BH) horses by means of histochemical analysis with m-ATPase and NADH-TR according to the sex and the biopsy depth. It was observed that the frequency (F; percent) and the relative cross sectional area (RCSA; percent) of the fibers type IIX were greater than the fibers type IIA, which F and RCSA were greater than the fibers type I. The comparison between sex and muscles depht, showed no significant difference in F and RCSA in the three types of fibers. The results of morphometry showed that the gluteus medius muscle has greater glycolitic metabolism and anaerobic capacity because of the presence of large proportion of type IIX fibers. This may be justified by the genetic influence of Thoroughbred in the formation of Brasileiro de Hipismo breed.

Fetal myocardial hypertrophy in an experimental model of gestational diabetes.

INTRODUCTION: The frequent occurrence of prenatal hypertrophy of the muscular ventricular septum has been widely reported in fetuses of diabetic mothers. OBJECTIVES: This experimental study was carried out to test the hypothesis that the weight of the heart, the ratio of the cardiac weight to that of the body, the thickness of the muscular ventricular septum, and the myocytic profile within the ventricular septum are all increased in fetuses of diabetic rats in comparison to fetuses of normal rats. METHODS: Diabetes was induced in 5 pregnant Wistar rats, bearing 30 fetuses, on the eighth day after conception, by intraperitoneal injection of 50 mg/kg of streptozotocin. Five normal pregnant Wistar rats, bearing 20 fetuses, made up the control group. Morphometric data were obtained by a computer-assisted method applied to the measurements of the thickness of the ventricular septum, and myocytic nuclear area. Statistical analysis utilized Student's t-test and Kruskal-Wallis test. RESULTS: The mean thickness of the septum was 675.56 microm (+/-159) in the control fetuses, and 904.39 microm (+/-262) in the fetuses carried by diabetic mothers (p < 0.001). The cardiac weight was 0.016 g (+/-0.004) in the control group, and 0.023 g (+/-0.005) in the group of diabetic fetuses (p < 0.001). The ratio of cardiac to body weight was 0.294% (+/-0.079) in the control group, and 0.514% (+/-0.073) in the diabetic group (p < 0.001). The myocytic nuclear area was 14.70 microm2 in the control group, and 21.43 microm2 in the diabetic group (p < 0.001). CONCLUSIONS: The presence of cellular and morphologic cardiac hypertrophy in fetuses of diabetic rats was demonstrated by the significant difference between the two groups for each analyzed feature.

[Participant survey in the intervention of intestinal helminthiasis transmission (satellite city of Paranoá -- Federal District]. / Pesquisa participante na intervenção da transmissão de helmintoses intestinais (Cidade Satélite do Paranoá-Distrito Federal).

This work was developed in the Paranoá city town of the Federal District of Brazil. It used techniques of participative research with the aim of reducing intestinal helminths transmission in a group of children at nutritional risk. The family nucleus, that is, parents, children and other relatives living together in the same house, was used as reference for this research. All steps of the work were followed simultaneously by technical and educative actions. The technical actions were related to faecal examinations and medication. The educative process, stimulated critical analysis and reflections on the central problem and life conditions, with a strong focus on Health Promotion to improve life quality, as well as an empowerment process. During the work development, of the action program included the following steps: home visits, interviews, group meetings, feedback on the faeces examinations results and treatment. An evaluation of the final results was made through quantitative and qualitative methods, which showed the construction, acquisition and socialisation of knowledge.