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Streamlit is an open-source Python coding framework for building web-applications or "web-apps" and is now being used by researchers to share large data sets from published studies and other resources. Here we present Stmol, an easy-to-use component for rendering interactive 3D molecular visualizations of protein and ligand structures within Streamlit web-apps. Stmol can render protein and ligand structures with just a few lines of Python code by utilizing popular visualization libraries, currently Py3DMol and Speck. On the user-end, Stmol does not require expertise to interactively navigate. On the developer-end, Stmol can be easily integrated within structural bioinformatic and cheminformatic pipelines to provide a simple means for user-end researchers to advance biological studies and drug discovery efforts. In this paper, we highlight a few examples of how Stmol has already been utilized by scientific communities to share interactive molecular visualizations of protein and ligand structures from known open databases. We hope Stmol will be used by researchers to build additional open-sourced web-apps to benefit current and future generations of scientists.
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OBJECTIVE: To explore the relationship between scores on the Test Your Memory (TYM) battery and findings from a more exhaustive neurocognitive assessment. METHODS: The TYM and fourteen psychometric tests were administered to 84 subjects aged 50 or older who attended an outpatient neurology clinic due to cognitive symptoms. Each patient's cognitive state was determined independently from his/her score on the TYM (CDR 0, n=25; CDR 0.5, n=45; CDR 1, n=14). We analysed concurrent validity of TYM scores and results from the psychometric tests, as well as the degree of concordance between the two types of measurement, by contrasting normalised data from each instrument. RESULTS: Although the intraclass correlation coefficient was 0.67 (confidence interval 95%, 0.53-0.77), analysis of the Bland-Altman plot and the curve on the survival-agreement plot (Luiz et al. method) demonstrates that the individual distances between the two methods exhibit excessive dispersion from a clinical viewpoint. TYM-based predictions of the mean z-score on psychometric tests differed substantially from real results in 30% of the subjects. Concordance of 95% can only be achieved by accepting absolute inter-instrument differences of up to 0.87 as identical values. Furthermore, the TYM underestimates cognitive performance for low values and overestimates it for high values. CONCLUSIONS: The TYM is a cognitive screening test which should not be used to predict results on psychometric tests or to detect cognitive changes in clinical trials.
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Memória/fisiologia , Testes Neuropsicológicos/normas , Psicometria , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/complicações , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Feminino , Humanos , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
OBJECTIVE: To determine the prospective validity of Test Your Memory (TYM) and its sensitivity to change in cognitive state. METHODS: This longitudinal prospective study followed 71 patients with subjective cognitive symptoms and 48 with mild cognitive impairment for a mean time period of 35.2 ± 15 months. Subjects did not have dementia or depression at the beginning of follow-up and each participant was given the TYM at least two times. A psychometric threshold was established to determine presence of a cognitive deficit (z-score ≤ 1.5 on at least one cognitive domain) and the Disability Assessment for Dementia scale was used to ensure full functional ability. The criterion for deterioration was a change in the stage on the Global Deterioration Scale. RESULTS: Sixty-one patients remained cognitively stable and 58 worsened. There were no differences between them with respect to sex, educational attainment, the initial stage on the GDS, or the score on the first TYM. Subjects who worsened were older than those who did not. The TYM increased an average of 0.04 points per month in patients who remained stable or improved (95% CI, -0.01 to 0.08) and decreased an average of 0.14 points per month in those whose condition worsened (95% CI, -0.19 to -0.09). Subjects with mild cognitive impairment who worsened displayed a sharper loss of TYM points than did subjects with subjective cognitive symptoms. CONCLUSIONS: While the TYM lacks prospective validity, it is sensitive to changes in cognitive state.
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Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia , Testes Neuropsicológicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To validate a Spanish version of the TYM, a self-administered cognitive screening test designed for the detection of Alzheimer's disease and mild cognitive defect. METHODS: A cross-sectional study was conducted in a neurology outpatient clinic. The TYM was administered to individuals of 50 years o more who came to the clinic for whatever the symptom. Their cognitive state was evaluated regardless of the outcome of TYM. They were categorized into 3 groups: 1) Cognitively normal (739), 2) with mild cognitive impairment (183), 3) with dementia (127). An analysis of items was made and the psychometric properties of the TYM were defined. There was a cross-validation, and the predictive validity of the TYM score, adjusted to the demographic variables, was determined by evaluating their performance in ROC curves. RESULTS: The internal consistency, interobserver reliability, short term and long-term test-retest reliability were adequate. The TYM correlated with the MMSE (r=0.779, P<.0001). The cross validation showed consistent results. With the TYM Score adjusted according to the educational level, a sensitivity of 0.86 with a specificity of 0.88 in the cut-off point of ≤40/50 was obtained to identify subjects with cognitive impairment, and a sensitivity of 0.94 with a specificity of 0.89 in the cut-off point of ≤36/50 to identify subjects with dementia. CONCLUSIONS: The TYM is a self-administered global cognitive test, possessing excellent psychometric properties and good predictive validity. It can be used as a cognitive screening test in subjects with 4 years or more of formal education.
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Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia , Testes Neuropsicológicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Estudos Transversais , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: To analyze the outcomes, predictors of success and predictors of need for hospital admission in our series of patients who underwent ureteroscopy (URS) as a major outpatient surgery (MOS) procedure. METHODS: We carried out a retrospective analysis of 402 patients who had undergone semi-rigid URS for ureteral calculi as a MOS procedure in our center between 2004 and 2012. Patients with previous DJ catheter were excluded. We classified the calculi according to their location (lumbar, pelvic, iliac), size (< or> 1cm) and number (single or multiple). Follow-up was done by plain X-ray of the abdomen and ultrasound one month after surgery. The procedure was considered successful when patients were free from the treated calculi or had ureteral fragments < 3 mm one month after surgery. Univariate and multivariate analyses were carried out to identify the factors involved in success and hospitalization not being required. RESULTS: A total of 269 patients were included. The majority of the stones were single (92.2%), <1 cm in size (76.6%), pelvic (62.1%), and left-sided (57.2%). 89.6% of the procedures were performed as MOS and 82.2% were considered to be successful. In the multivariate analysis, left-sided (p<0.001) and pelvic location of the calculi (p=0,01) were found to be independent predictors for the success of the procedure In terms of hospital admission, the only independent predictor was the presence of intraoperative complications ( p=0.006). CONCLUSIONS: Left-sided and pelvic locations were the independent predictors for the success of the URS. A lack of intraoperative complications was the independent predictor for not requiring hospitalisation.
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Cálculos Ureterais/cirurgia , Ureteroscopia/métodos , Adulto , Procedimentos Cirúrgicos Ambulatórios , Anestesia Geral , Feminino , Hospitalização , Humanos , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJETIVO: La ureteroscopia constituye una opción con elevadas tasas de éxito en el tratamiento de los cálculos ureterales, siendo superiores a la litotricia en la mayoría de los casos. El objetivo de nuestro trabajo es analizar las variables clínicas y demográficas, resultados y complicaciones, de nuestra serie de pacientes sometidos a ureteroscopia en régimen de cirugía mayor ambulatoria (CMA) y analizar los factores predictores de éxito del tratamiento y necesidad de ingreso hospitalario. MÉTODOS: Analizamos de forma retrospectiva 402 pacientes sometidos a ureteroscopia semirrígida (URS) por litiasis ureteral en régimen de CMA en nuestro centro entre 2004 y 2012. Excluimos los pacientes con catéter doble jota (CDJ) previo. Clasificamos las litiasis según su localización (lumbar, iliaca, pélvica) tamaño (< o > 1cm) y número (única o múltiple). El tratamiento se realizó mediante extracción con pinzas, LASER Holmium, o fragmentación mecánica. La revisión se realizó mediante radiografía simple de abdomen y ecografía al mes de la intervención. Consideramos éxito del procedimiento los pacientes libres del cálculo tratado o con restos litiásicos ureterales <3 mm al mes de la intervención. Realizamos un análisis univariante y multivariante mediante chi cuadrado y regresión logística para identificar los factores implicados en el éxito y la no necesidad de hospitalización. RESULTADOS: Incluimos 269 pacientes, 59% varones. La mayoría de la litiasis fueron únicas (92,2%), menores de un centímetro (76,6%), de localización pélvica (62,1%) e izquierdas (57,2%). Realizamos dilatación neumática del orificio ureteral en 67,3% de los casos, tratamos la mayoría de las litiasis con LASER (48%) y dejamos CDJ postoperatorio en el 92,2% de los casos. En el 83,3% de los procedimientos no existieron complicaciones intraoperatorias, realizándose el 89,6% en CMA, considerándolo éxito en el 82,2%. En el análisis multivariante, la lateralidad izquierda (p<0,001) y la localización pélvica de la litiasis (p=0,01) resultaron factores predictivos independientes de éxito del procedimiento. Para la necesidad de ingreso hospitalario solo la ausencia de complicaciones intraoperatorias resulto factor predictivo independiente (p=0,006). CONCLUSIONES: La lateralidad izquierda y la localización pélvica constituyen los factores predictores independientes de éxito de la URS. La ausencia de complicaciones intraoperatorias constituye el factor predictor independiente de no precisar hospitalización (AU)
OBJECTIVES: To analyze the outcomes, predictors of success and predictors of need for hospital admission in our series of patients who underwent ureteroscopy (URS) as a major outpatient surgery (MOS) procedure. METHODS: We carried out a retrospective analysis of 402 patients who had undergone semi-rigid URS for ureteral calculi as a MOS procedure in our center between 2004 and 2012. Patients with previous DJ catheter were excluded. We classified the calculi according to their location (lumbar, pelvic, iliac), size (< or > 1cm) and number (single or multiple). Follow-up was done by plain X-ray of the abdomen and ultrasound one month after surgery. The procedure was considered successful when patients were free from the treated calculi or had ureteral fragments <3 mm one month after surgery. Univariate and multivariate analyses were carried out to identify the factors involved in success and hospitalization not being required. RESULTS: A total of 269 patients were included. The majority of the stones were single (92.2%), <1 cm in size (76.6%), pelvic (62.1%), and left-sided (57.2%). 89.6% of the procedures were performed as MOS and 82.2% were considered to be successful. In the multivariate analysis, left-sided (p<0.001) and pelvic location of the calculi (p=0,01) were found to be independent predictors for the success of the procedure In terms of hospital admission, the only independent predictor was the presence of intraoperative complications (p=0.006). CONCLUSIONS: Left-sided and pelvic locations were the independent predictors for the success of the URS. A lack of intraoperative complications was the independent predictor for not requiring hospitalisation (AU)
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Humanos , Ureterolitíase/cirurgia , Ureteroscopia/métodos , Hospitalização/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Dilatação , LitotripsiaRESUMO
The aim of this study was to evaluate the IgG activity in serum and milk samples of experimentally infected lactating ewes with the nematode Teladorsagia circumcincta as well as its relationship to the degree of infection. In a previous study 28 pregnant ewes were divided into two homogeneous groups, with high (H) and low (L) level of parasitism, respectively. Blood and milk samples were taken weekly after lambing until the end of the lactation, 126 days post-partum (pp). IgG against T. circumcincta were measured by means of an indirect ELISA. The kinetic of the immunoglubulins in serum samples showed a very low activity at the beginning but gradually increased throughout the lactation; H group showed higher values most of the sampled days than L group. Contrary, IgG in milk samples remained high during the first month pp, then decreased around 38% and by the end of the study rose again. Antibodies in both samples were correlated and especially during the second month of lactation (r=0.3; p<0.001). With the aim to correlate the immune response and the degree of infection we found an inverse relationship (r=-0.2; p<0.05) during the second month of lactation between eggs and IgG in serum. However the correlation with immunoglobulins in milk was positive, mainly, on the last third of lactation (r=0.2; p<0.01). As a conclusion, the individual detection of total IgG antibodies against T. circumcincta in lactating ewes is highly dependent on the stage of lactation. Therefore, these associations should be confirmed under field conditions.
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Anticorpos Anti-Helmínticos/sangue , Leite/imunologia , Doenças dos Ovinos/imunologia , Trichostrongyloidea/imunologia , Tricostrongiloidíase/veterinária , Animais , Anticorpos Anti-Helmínticos/análise , Ensaio de Imunoadsorção Enzimática/veterinária , Fezes/parasitologia , Feminino , Imunoglobulina G/sangue , Lactação/imunologia , Contagem de Ovos de Parasitas/veterinária , Gravidez , Ovinos , Doenças dos Ovinos/parasitologia , Tricostrongiloidíase/imunologia , Tricostrongiloidíase/parasitologiaRESUMO
Infection by gastrointestinal nematodes (GIN) in grazing sheep can negatively influence the growth of lambs and milk yield. In the current study we evaluated the effect of high and low levels of infection with Teladorsagia circumcincta on production parameters of lactating ewes. Two groups of ewes were infected with 50,000 T. circumcincta third stage larvae (L3) 30 days before lambing. To obtain a high level of infection, Group HI was challenged with 30,000 L3 30 days post-partum (pp) and again 90 days pp with the same dose. The low infection group (LI) was treated with an intraruminal controlled-release albendazole bolus one-month pp. We determined the effect of the differing parasite loads on milk yield, milk composition, weight gain, and body condition (BC). Throughout the trial the milk yield was higher in the LI group and, consequently, at the end of the lactation, this group produced 11.1% more milk than the HI group. In the final third of lactation there was an overall increase in milk fat, protein, and lactose although the factor most affected by infection level was the protein percentage, with an increment of 11.9% in the HI group. The somatic cell counts remained low during the experiment indicating the absence of udder infection. Regarding weight and BC, significant differences were found only in BC although LI ewes weighed 2% more than the HI group. In conclusion, a low level of GIN infection in sheep leads to a better BC and a higher milk production with high protein percentage.
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Lactação , Leite/química , Nematoides/classificação , Infecções por Nematoides/veterinária , Doenças dos Ovinos/parasitologia , Animais , Composição Corporal , Peso Corporal , Indústria de Laticínios , Fezes/parasitologia , Feminino , Infecções por Nematoides/parasitologia , Infecções por Nematoides/patologia , Contagem de Ovos de Parasitas , Ovinos , Doenças dos Ovinos/patologiaRESUMO
In total, 140 populations of the genus Meloidogyne collected from representative horticultural regions of Spain and maintained at the Department of Agroecology, Institute of Agrarian Sciences, Madrid were characterized using perineal morphology, sequenced characterized amplified region polymerase chain reaction with species-specific primers, and bioassay. Using a modified North Carolina differential host test as a basis, 13 Meloidogyne populations did not fit into the published race scheme. These populations had very limited host ranges, reproducing only on susceptible tomato cv. Marmande and sometimes also on tobacco cv. NC95 and the pepper cv. Sonar in the case of Meloidogyne arenaria. They did not reproduce on cotton or peanut. The species and new races were identified as M. incognita races 5 (6 populations) and 6 (2 populations) and M. javanica race 5 (2 populations), with new records of M. arenaria race 3 (2 populations) and M. javanica race 1 (23 populations) for Spain.
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The diffusive relaxation of a colloidal fluid adsorbed in a porous medium depends on many factors, including the concentration and composition of the adsorbed colloidal fluid, the average structure of the porous matrix, and the nature of the colloid-colloid and colloid-substrate interactions. A simple manner to describe these effects is to model the porous medium as a set of spherical particles fixed in space at random positions with prescribed statistical structural properties. Within this model one may describe the relaxation of concentration fluctuations of the adsorbed fluid by simply setting to zero the short-time mobility of one species (the porous matrix) in a theory of the dynamics of equilibrium colloidal mixtures, or by extending such dynamic theory to explicitly consider the porous matrix as a random external field, as recently done in the framework of mode coupling theory [V. Krakoviack, Phys. Rev. Lett. 94, 065703 (2005)]. Here we consider the first approach and employ the self-consistent generalized Langevin equation (SCGLE) theory of the dynamics of equilibrium colloidal mixtures, to describe the dynamics of the mobile component. We focus on the short- and intermediate-time regimes, which we compare with Brownian dynamics simulations involving a binary mixture with screened Coulomb interactions for two models of the average static structure of the matrix: a porous matrix constructed by quenching configurations of an equilibrium mixture in which both species were first equilibrated together, and a preexisting matrix with prescribed average structure, in which we later add the mobile species. We conclude that in both cases, if the correct static structure factors are provided as input, the SCGLE theory correctly predicts the main features of the dynamics of the permeating fluid.
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This paper presents a recently developed theory of colloid dynamics as an alternative approach to the description of phenomena of dynamic arrest in monodisperse colloidal systems. Such theory, referred to as the self-consistent generalized Langevin equation (SCGLE) theory, was devised to describe the tracer and collective diffusion properties of colloidal dispersions in the short- and intermediate-time regimes. Its self-consistent character, however, introduces a nonlinear dynamic feedback, leading to the prediction of dynamic arrest in these systems, similar to that exhibited by the well-established mode coupling theory of the ideal glass transition. The full numerical solution of this self-consistent theory provides in principle a route to the location of the fluid-glass transition in the space of macroscopic parameters of the system, given the interparticle forces (i.e., a nonequilibrium analog of the statistical-thermodynamic prediction of an equilibrium phase diagram). In this paper we focus on the derivation from the same self-consistent theory of the more straightforward route to the location of the fluid-glass transition boundary, consisting of the equation for the nonergodic parameters, whose nonzero values are the signature of the glass state. This allows us to decide if a system, at given macroscopic conditions, is in an ergodic or in a dynamically arrested state, given the microscopic interactions, which enter only through the static structure factor. We present a selection of results that illustrate the concrete application of our theory to model colloidal systems. This involves the comparison of the predictions of our theory with available experimental data for the nonergodic parameters of model dispersions with hard-sphere and with screened Coulomb interactions.
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Fresh crop and garden residues were applied both under laboratory conditions and in commercial greenhouse in order to asses their effect on soil nematodes populations and soil fertility. In the laboratory experiments, dosages of 5 to 20 g of cabbage residues, chicken manure, cabbage residues+chicken manure, grass+chicken manure, as well as leaves and stems of orange tree, pine tree, oleander, olive tree, palm tree and boxwood were mixed with 500 g soil having root-knot nematodes (Meloidogyne incognita) and soil moisture was adjusted at field capacity. A control treatment without residues was also included. The mixtures were kept into plastic bags, with four replications, and the bags were incubated for four weeks at 30 degrees C, when nematological and soil fertility analyses were carried out. In general, all these materials significantly (P < 0.05) reduced M. incognita populations and increased saprophagous nematodes, with slight effects on soil fertility except for the K increase with residues application. Tomato plants susceptible to M. incognita were planted in pots with 300 cm3 of the treated soils and kept for five weeks in a growth chamber (24 +/- 1 degrees C, 14 hours light), when root galling indices were evaluated. Most materials applied reduced root galling indices as regards to the control. In the greenhouse experiment, cabbage residues, cabbage residues+chicken manure, grass+chicken manure and grass+cabbage residues were applied to the soil and covered with a polyethylene sheet for 5 weeks. A cabbage residues:chicken manure treatment and a control (not-amended) treatment, without polyethylene, were also included. At the end of the experiment, the nematological analysis showed that all materials successfully controlled M. incognita populations, reaching 86-100% mortality with organic amendments vs. 6% for the control. After the greenhouse biodesinfestation experiment, a tomato crop was grown for one month, when root galling indices were determined. All materials significantly reduced this value from 4.75 in the control to 1.0-2.25 with the organic amendments, except for the cabbage residues+chicken manure treatment without polyethylene (index = 4.0). Our results show that fresh crop and garden residues successfully reduced M. incognita populations and root galling indices when applied with polyethylene covers, having good potential to be considered in integrated management programs.
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Controle Biológico de Vetores/métodos , Solo/parasitologia , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/parasitologia , Tylenchoidea/crescimento & desenvolvimento , Animais , Biodegradação Ambiental , Brassica , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/parasitologia , Esterco , Raízes de Plantas/parasitologia , Solo/normas , Especificidade da EspécieRESUMO
One of the main elements of the self-consistent generalized Langevin equation (SCGLE) theory of colloid dynamics [Phys. Rev. E 62, 3382 (2000); 72, 031107 (2005)] is the introduction of exact short-time moment conditions in its formulation. The need to previously calculate these exact short-time properties constitutes a practical barrier for its application. In this Brief Report, we report that a simplified version of this theory, in which this short-time information is eliminated, leads to the same results in the intermediate and long-time regimes. Deviations are only observed at short times, and are not qualitatively or quantitatively important. This is illustrated by comparing the two versions of the theory for representative model systems.
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The biofumigant effect of pepper crop residues (PCR) for controlling Meloidogyne incognita populations was evaluated. Under laboratory conditions, 0, 5, 10 and 20 g PCR were applied to 500 g nematode infested soil, with four replicates per treatment. After 20 days at 25 degrees C, PCR reduced significantly M. incognita populations and root galling indices in susceptible tomato cv. Marmande, and increased K, N and organic C in soil. In the field, biofumigation with PCR combined with fresh animal manures (with and without plastic cover), methyl bromide, and a control were evaluated through root galling indices on a pepper crop. Each treatment, except for the control, had a grafted and non-grafted susceptible pepper sub-treatment, with three replicates. Root galling indices were lower, and yields higher, on grafted plants, biofumigation with PCR and plastic cover, with similar values as MB treatment, suggesting that biofumigation with PCR is an efficient non-chemical alternative to control M. incognita populations, especially when applied with plastic cover, nitrogen-rich organic matter and followed by grafting on resistant pepper.
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Produtos Agrícolas , Nematoides , Controle Biológico de Vetores , Raízes de Plantas/parasitologia , AnimaisRESUMO
A survey to determine the prevalence of anthelmintic resistance in nematode parasites of sheep against the three main families of anthelmintics (benzimidazoles, macrocyclic lactones and imidazothiazoles) was carried out from January 1999 to December 2003 involving 85 flocks in Northwest (NW) Spain. In the study on prevalence of resistance to benzimidazoles, faecal egg count reduction test (FECRT) showed there was resistance in 8 (12.7%) flocks, 1 (1.6%) was suspected, and 54 (85.7%) were susceptible. The results indicated that 9 flocks (34.61%) showed resistance, 1 (3.85%) showed suspected resistance, and 16 (61.54%) were susceptible to the imidazothiazoles. Against macrocyclic lactones, resistance was observed in 8 flocks (15.69%), 4 (7.84%) showed suspected resistance and 39 (76.47%) were susceptible. None of the flocks used in the study showed resistance to the three families of anthelmintics. Nevertheless, six were recorded as resistant or suspected of being resistant to two of these families of anthelmintics. Egg hatch assay (EHA) and FECRT were carried out jointly on 61 flocks, although EHA was done on a total of 83 farms. The results showed that 15 (18.07%) of the 83 flocks were resistant, with egg death 50 over 0.1 microg/ml thiabendazole, and 68 (81.93%) were susceptible to benzimidazoles. When the results between FECRT and EHA were compared, both techniques showed good correlation in field studies. Faecal cultures performed pre- and post-treatment indicated that Teladorsagia and Trichostrongylus were the main genera.
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Anti-Helmínticos/farmacologia , Resistência a Medicamentos , Tricostrongilose/prevenção & controle , Trichostrongylus/efeitos dos fármacos , Animais , Benzimidazóis/farmacologia , Coleta de Dados , Resistência a Múltiplos Medicamentos , Fezes/parasitologia , Macrolídeos/farmacologia , Contagem de Ovos de Parasitas , Parasitologia/métodos , Distribuição Aleatória , Ovinos/parasitologia , Espanha , Trichostrongylus/isolamento & purificaçãoRESUMO
Nigrin b is a non-toxic type 2 ribosome-inactivating protein as active as ricin at ribosomal level but 10(5) and 5 x 10(3) times less toxic for animal cell cultures and mice, respectively, than ricin. The purpose of the present study was to analyze the effects of intravenous injection of large amounts of nigrin b to the mouse. Injection through the tail vein of 16 mg/kg body weight killed all mice studied before 2 days. Analysis of several major tissues by light microscopy did not reveal gross nigrin b-promoted changes, except in the intestines which appeared highly damaged. As a consequence of the injury, the villi and crypt structures of the small intestine disappeared, leading to profuse bleeding and death. In contrast, intravenous injection of 5 mg/kg body weight was not lethal to mice but did trigger reversible toxic effects. In both cases, lethal and sub-lethal doses, the target of nigrin b appeared to be the highly proliferating stem cells of the intestinal crypts, which had undergone apoptotic changes. In contrast to nigrin b, the injection of 3 mug/kg of ricin kills all mice in 5 days but does not trigger apoptosis in the crypts. Therefore, the effect seen with sub-lethal nigrin b concentrations seems to be specific. Nigrin b killed COLO 320 human colon adenocarcinoma cells with an IC(50) of 3.1 x 10(-8) M and the effect was parallel to the extent of DNA fragmentation of these cells. Accordingly, despite the low general toxicity exerted by nigrin b as compared with ricin, intravenous injection of large amounts of nigrin b is able to kill mouse intestinal stem cells without threatening the lives of the animals, thereby opening a door for its use for the targeting of intestinal stem cells.
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Intestino Delgado/efeitos dos fármacos , N-Glicosil Hidrolases/toxicidade , Proteínas de Plantas/toxicidade , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Injeções Intravenosas , Intestino Delgado/patologia , Camundongos , Proteínas Inativadoras de Ribossomos Tipo 2 , Ricina/toxicidade , Células-Tronco/efeitos dos fármacosRESUMO
SUMMARY Previous experiments have shown that genetic resistance to infection by Teladorsagia circumcincta in sheep can be measured by the level of IgA in gastric mucus, jointly with other parameters. The aim of this study has been to observe the influence of IgA on adult worms. The experiment was carried out with Churra sheep experimentally infected with T. circumcincta. At slaughter, gastric content, gastric mucus, blood samples and faeces were recovered to determine the number of eggs in utero, length of adult females, worm burden, number of L4, titre of serum pepsinogen, peripheral eosinophilia and eggs per gram (epg). IgA activity in gastric mucus, serum, nasal secretions and saliva were tested against somatic antigen from fourth-stage larvae (L4), somatic antigen from the adult stage and excretory-secretory (E/S) antigen from the adult stage. The results showed a significant correlation between serum IgA and gastric mucus (P<0.01) as well as in nasal secretions (P<0.01). We found negative correlations between IgA activity in gastric mucus with the eggs in utero and with adult female length. Furthermore there were also strong relationships between the peripheral eosinophilia with serum (P<0.01) and gastric mucus IgA activity (P<0.01). Moreover serum pepsinogen and the number of L4 at slaughter were related (P<0.01).
Assuntos
Anticorpos Anti-Helmínticos/imunologia , Gastroenteropatias/veterinária , Imunoglobulina A/imunologia , Doenças dos Ovinos/parasitologia , Ovinos/imunologia , Trichostrongyloidea/imunologia , Tricostrongiloidíase/veterinária , Animais , Anticorpos Anti-Helmínticos/sangue , Ensaio de Imunoadsorção Enzimática/veterinária , Eosinofilia/parasitologia , Eosinofilia/veterinária , Fezes/parasitologia , Feminino , Mucosa Gástrica/imunologia , Mucosa Gástrica/parasitologia , Gastroenteropatias/imunologia , Gastroenteropatias/parasitologia , Imunidade Inata/genética , Imunoglobulina A/sangue , Mucosa Nasal/imunologia , Mucosa Nasal/parasitologia , Contagem de Ovos de Parasitas/veterinária , Parasitemia/sangue , Parasitemia/imunologia , Parasitemia/parasitologia , Parasitemia/veterinária , Pepsinogênio A/sangue , Distribuição Aleatória , Saliva/imunologia , Saliva/parasitologia , Ovinos/genética , Doenças dos Ovinos/genética , Doenças dos Ovinos/imunologia , Tricostrongiloidíase/sangue , Tricostrongiloidíase/imunologia , Tricostrongiloidíase/parasitologiaRESUMO
SUMMARY The aim of this study was to understand the influence of a low protein diet on the resistance of the Churra breed sheep to infection with Teladorsagia circumcincta. A previous experiment in our department demonstrated significant differences between resistant and susceptible sheep infected with T. circumcincta, in eggs per gram of faeces, serum pepsinogen, serum IgA and peripheral eosinophilia (unpublished). The sheep were fed with a balanced protein diet. In the current assay there were significant differences between the resistant and susceptible groups in egg output, serum pepsinogen and worm burden. The optical densities (OD) of the IgA in blood samples, nasal secretions and saliva were tested throughout the study and the differences between groups were not significant. At necropsy adult worm length, the number of eggs in utero in adult females, the number of fourth stage larvae and the OD of gastric mucus IgA did not differ between groups either. Moreover, due to diet there was a loss of weight in both groups but this was not significant. Our results support the view that low protein diets could influence immune function and as a result resistant genotypes do not show any superiority in comparison with susceptible ones.
Assuntos
Proteínas Alimentares/farmacologia , Gastroenteropatias/veterinária , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/parasitologia , Ovinos/imunologia , Trichostrongyloidea/imunologia , Tricostrongiloidíase/veterinária , Animais , Anticorpos Anti-Helmínticos/sangue , Proteínas Alimentares/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Eosinofilia/parasitologia , Eosinofilia/veterinária , Fezes/parasitologia , Feminino , Gastroenteropatias/imunologia , Gastroenteropatias/parasitologia , Imunidade Inata/fisiologia , Imunoglobulina A/sangue , Mucosa Nasal/parasitologia , Estado Nutricional/fisiologia , Contagem de Ovos de Parasitas/veterinária , Pepsinogênio A/sangue , Saliva/parasitologia , Tricostrongiloidíase/imunologia , Tricostrongiloidíase/parasitologiaRESUMO
This report describes a new molecular method for the diagnosis of benzimidazole susceptibility or resistance in three main species of trichostrongylids of sheep (Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus vitrinus). This assay is based on the use of real time polymerase chain reaction (PCR) to detect mutations of residue 200 on isotype 1 of beta-tubulin. The technique allows calculation of the proportion of each allelic variant as it combines kinetic (real time quantitative) PCR with allele-specific amplification and requires no post-PCR processing. The level of resistance in the population is determined by the proportion of the beta-tubulin codon 200 TAC allele. Hence, it was observed that the proportion of the resistant allele in susceptible strains ranged between 24% and 32.3%; in resistant strains this value increased to between 71.3% and 86.3%. Furthermore, there was a good correlation between real time PCR, faecal egg count reduction test, egg hatch assay and conventional allele-specific PCR, in both resistant and susceptible strains. A sensitive, rapid, highly reproducible and inexpensive technique for detecting resistance to benzimidazoles in a worm population has been developed.
Assuntos
Antinematódeos/farmacologia , Benzimidazóis/farmacologia , Gastroenteropatias/veterinária , Doenças dos Ovinos/parasitologia , Trichostrongyloidea/genética , Tricostrongiloidíase/veterinária , Animais , DNA de Helmintos/química , DNA de Helmintos/genética , Resistência a Medicamentos/genética , Fezes/parasitologia , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/parasitologia , Contagem de Ovos de Parasitas/veterinária , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Nucleotídeo Único/genética , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Trichostrongyloidea/efeitos dos fármacos , Trichostrongyloidea/isolamento & purificação , Tricostrongiloidíase/tratamento farmacológico , Tricostrongiloidíase/parasitologia , Tubulina (Proteína)/química , Tubulina (Proteína)/genéticaRESUMO
Ribosome-inactivating proteins (RIPs) are a family of enzymes that trigger the catalytic inactivation of ribosomes. The most known member of the family is the highly poisonous two-chain ricin isolated from Ricinus communis L. Sambucus species contain a number of two-chain RIPs structurally and enzymatically related to ricin which have the noteworthy feature that, having an enzymatic activity on ribosomes, leading to the inhibition of protein synthesis, higher than ricin, they are lacking of the tremendous unspecific toxicity of ricin. Therefore, they have been called non-toxic type 2 RIPs. The most representative and studied members are nigrin b present in the bark of the common (black) elder Sambucus nigra L. and ebulin 1 present in the leaves of the dwarf elder Sambucus ebulus L. The molecular basis for the low unspecific activities of nigrin b and ebulin 1 as compared with ricin seems to be related with single changes of amino acids in the high affinity sugar binding sites of the B chains. These changes determine the intracellular traffic of these proteins and thus the cellular toxicity. Conjugation ofnigrin b or ebulin 1 to either transferrin or monoclonal antibodies provided highly active conjugates targeting cancer. Thus these non-toxic type 2 RIPs are promising tools for cancer therapy.