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1.
SAR QSAR Environ Res ; 33(1): 49-61, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35048766

RESUMO

The enzyme acetylcholinesterase (AChE) is currently a therapeutic target for the treatment of neurodegenerative diseases. These diseases have highly variable causes but irreversible evolutions. Although the treatments are palliative, they help relieve symptoms and allow a better quality of life, so the search for new therapeutic alternatives is the focus of many scientists worldwide. In this study, a QSAR-SVM classification model was developed by using the MATLAB numerical computation system and the molecular descriptors implemented in the Dragon software. The obtained parameters are adequate with accuracy of 88.63% for training set, 81.13% for cross-validation experiment and 81.15% for prediction set. In addition, its application domain was determined to guarantee the reliability of the predictions. Finally, the model was used to predict AChE inhibition by a group of quinazolinones and benzothiadiazine 1,1-dioxides obtained by chemical synthesis, resulting in 14 drug candidates with in silico activity comparable to acetylcholine.


Assuntos
Doença de Alzheimer , Inibidores da Colinesterase , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Humanos , Ligantes , Simulação de Acoplamento Molecular , Qualidade de Vida , Relação Quantitativa Estrutura-Atividade , Reprodutibilidade dos Testes
2.
J Surg Case Rep ; 2021(12): rjab548, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34909173

RESUMO

Gastric volvulus is a rare condition defined as an abnormal stomach rotation around its axis, which usually presents in children under a year or in adults in their fifth decade. Cases over 70-year-old are rare and only 30% of cases of this disease present with mesenteric-axial rotation of the stomach. In this article, we report a rare case of mesenteroaxial gastric volvulus associated with hiatal hernia, in an 88-year-old woman, who presented to the Emergency Department of our institution with bowel obstruction symptoms. The diagnosis could be difficult due to the rarity of the pathology, the patient's age outside the expected incidence age range and the less common mesenteroaxial presentation. This report highlights the importance of the differential diagnosis of gastric volvulus as a cause of intestinal obstruction.

3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 1341-1344, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34891532

RESUMO

Parkinson's disease (PD) is considered a movement disease; it is a progressive and degenerative neurological disorder, causing disabling motor dysfunctions. Investigate the body instability of PD patients through the stabilometry test is the aim of this study. A sample of 40 participants with PD were staged between the stages of the disease using Hoehn and Yahr Modified Scale 1.5 to 3.0 in static posture with eyes open and closed to assess stabilometry in the distance from the center of pressure (CoP), as well as anteroposterior (AP) and mediolateral axis (ML). There were found no differences in the body oscillation variables on the AP and ML axis. There was a difference in CoP displacement and oscillation speed between stage 1.5 to 3.0. It was concluded that participants with PD in stage 3.0 had greater distances from the CoP and greater speed of body sway, and that these instabilities become more evident with the progression of the disease.


Assuntos
Doença de Parkinson , Humanos , Equilíbrio Postural , Postura
4.
Rev Neurol ; 73(12): 416-420, 2021 11 16.
Artigo em Espanhol | MEDLINE | ID: mdl-34877644

RESUMO

INTRODUCTION AND AIMS: Rituximab (RTX) is an anti-CD20 monoclonal antibody that has been used in cases of refractory myasthenia gravis (MG). The aim of this work is to analyse the efficacy and safety of RTX in MG in real clinical practice in a tertiary hospital. PATIENTS AND METHODS: A retrospective study was conducted with patients with MG treated with RTX in our centre from March 2014 to September 2020. Demographic and serological data, together with information about previous immunomodulatory treatment, clinical response and adverse effects are collected. RESULTS: Twenty patients with MG - 100% generalised: 70% late-onset MG (LOMG) and 30% early-onset MG (EOMG) - were given RTX (mean age: 66.8 years; 70% male). A total of 90% are seropositive, 16 of them with positive anti-acetylcholine receptor antibodies and two with positive muscle-specific tyrosine kinase (anti-MuSK) antibodies. All had failed previous treatments: 100% with steroids, 100% with intravenous immunoglobulins and/or plasmapheresis, 55% with other immunosuppressants (25% with one previous immunosuppressant, 10% with two, 15% with three and 5% with four) and 35% with thymectomy. After RTX, 75% of patients showed a clinical response (12 patients with complete remission and the possibility of steroid withdrawal without recurrence; and three patients with partial remission and the possible reduction of steroid dosage) and 25% therapeutic failure; in all these cases RTX was withdrawn. All the anti-MuSK+ patients (100%) and 92.8% of the LOMG patients responded to RTX, while 66% of EOMG patients failed. Only three patients reported adverse effects, all of which were mild and did not require RTX withdrawal. CONCLUSION: In our experience, rituximab is a safe and effective treatment in aggressive generalised MG with anti-MuSK or late-onset MG (LOMG).


TITLE: Rituximab para el tratamiento de la miastenia grave generalizada: experiencia en la práctica clínica.Introducción y objetivos. El rituximab (RTX) es un anticuerpo monoclonal anti-CD20 que se ha utilizado en casos de miastenia grave (MG) refractaria. El objetivo de este trabajo es analizar la eficacia y la seguridad del RTX en la MG en la práctica clínica real en un hospital terciario. Pacientes y métodos. Se realiza un estudio retrospectivo de pacientes con MG tratados con RTX en nuestro centro de marzo de 2014 a septiembre de 2020. Se recogen datos demográficos, serológicos, tratamiento inmunomodulador previo, respuesta clínica y efectos adversos. Resultados. Veinte pacientes con MG ­el 100%, generalizada: el 70%, MG de inicio tardío (LOMG), y el 30%, MG de inicio temprano (EOMG)­ han recibido RTX (edad media: 66,8 años; 70%, varones). El 90% son seropositivos ­16 con anticuerpos antirreceptor de la acetilcolina positivos y dos con anticuerpos antitirosincinasa muscular específica (anti-MuSK) positivos­. Todos habían fracasado con tratamientos previos: el 100% con esteroides, el 100% con inmunoglobulinas intravenosas y/o con plasmaféresis, el 55% con otros inmunosupresores (25%, un inmunosupresor previo; 10%, dos; 15%, tres; y 5%, cuatro) y el 35% con timectomía. Tras el RTX, presentó respuesta clínica el 75% de los pacientes (12 pacientes, remisión completa con posibilidad de la retirada de los esteroides sin recurrencia; y tres parcial, con posibilidad de la reducción de la dosis de esteroides) y fracaso terapéutico el 25%; en todos estos casos se retiró el RTX. El 100% de los pacientes anti-MuSK+ y el 92,8% de los de LOMG presentaron respuesta al RTX, mientras que el 66% de los pacientes con EOMG fracasaron. Sólo tres pacientes presentaron efectos adversos, todos leves, que no requirieron la retirada del RTX. Conclusión. En nuestra experiencia, el rituximab es un tratamiento seguro y eficaz en la MG generalizada agresiva con anticuerpos anti-MuSK o de inicio tardío (LOMG).


Assuntos
Miastenia Gravis/tratamento farmacológico , Rituximab/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Estudos Retrospectivos , Rituximab/efeitos adversos , Resultado do Tratamento
5.
Rev. neurol. (Ed. impr.) ; 73(12): 416-420, Dic 16, 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-229608

RESUMO

Introducción y objetivos: El rituximab (RTX) es un anticuerpo monoclonal anti-CD20 que se ha utilizado en casos de miastenia grave (MG) refractaria. El objetivo de este trabajo es analizar la eficacia y la seguridad del RTX en la MG en la práctica clínica real en un hospital terciario. Pacientes y métodos:Se realiza un estudio retrospectivo de pacientes con MG tratados con RTX en nuestro centro de marzo de 2014 a septiembre de 2020. Se recogen datos demográficos, serológicos, tratamiento inmunomodulador previo, respuesta clínica y efectos adversos. Resultados: Veinte pacientes con MG –el 100%, generalizada: el 70%, MG de inicio tardío (LOMG), y el 30%, MG de inicio temprano (EOMG)– han recibido RTX (edad media: 66,8 años; 70%, varones). El 90% son seropositivos –16 con anticuerpos antirreceptor de la acetilcolina positivos y dos con anticuerpos antitirosincinasa muscular específica (anti-MuSK) positivos–. Todos habían fracasado con tratamientos previos: el 100% con esteroides, el 100% con inmunoglobulinas intravenosas y/o con plasmaféresis, el 55% con otros inmunosupresores (25%, un inmunosupresor previo; 10%, dos; 15%, tres; y 5%, cuatro) y el 35% con timectomía. Tras el RTX, presentó respuesta clínica el 75% de los pacientes (12 pacientes, remisión completa con posibilidad de la retirada de los esteroides sin recurrencia; y tres parcial, con posibilidad de la reducción de la dosis de esteroides) y fracaso terapéutico el 25%; en todos estos casos se retiró el RTX. El 100% de los pacientes anti-MuSK+ y el 92,8% de los de LOMG presentaron respuesta al RTX, mientras que el 66% de los pacientes con EOMG fracasaron. Sólo tres pacientes presentaron efectos adversos, todos leves, que no requirieron la retirada del RTX. Conclusión: En nuestra experiencia, el rituximab es un tratamiento seguro y eficaz en la MG generalizada agresiva con anticuerpos anti-MuSK o de inicio tardío (LOMG).(AU)


Introduction and aims: Rituximab (RTX) is an anti-CD20 monoclonal antibody that has been used in cases of refractory myasthenia gravis (MG). The aim of this work is to analyse the efficacy and safety of RTX in MG in real clinical practice in a tertiary hospital. Patients and methods: A retrospective study was conducted with patients with MG treated with RTX in our centre from March 2014 to September 2020. Demographic and serological data, together with information about previous immunomodulatory treatment, clinical response and adverse effects are collected. Results: Twenty patients with MG – 100% generalised: 70% late-onset MG (LOMG) and 30% early-onset MG (EOMG) – were given RTX (mean age: 66.8 years; 70% male). A total of 90% are seropositive, 16 of them with positive anti-acetylcholine receptor antibodies and two with positive muscle-specific tyrosine kinase (anti-MuSK) antibodies. All had failed previous treatments: 100% with steroids, 100% with intravenous immunoglobulins and/or plasmapheresis, 55% with other immunosuppressants (25% with one previous immunosuppressant, 10% with two, 15% with three and 5% with four) and 35% with thymectomy. After RTX, 75% of patients showed a clinical response (12 patients with complete remission and the possibility of steroid withdrawal without recurrence; and three patients with partial remission and the possible reduction of steroid dosage) and 25% therapeutic failure; in all these cases RTX was withdrawn. All the anti-MuSK+ patients (100%) and 92.8% of the LOMG patients responded to RTX, while 66% of EOMG patients failed. Only three patients reported adverse effects, all of which were mild and did not require RTX withdrawal. Conclusion: In our experience, rituximab is a safe and effective treatment in aggressive generalised MG with anti-MuSK or late-onset MG (LOMG).(AU)


Assuntos
Humanos , Masculino , Feminino , Miastenia Gravis/tratamento farmacológico , Rituximab/administração & dosagem , Nervos Periféricos , Imunossupressores , Antígenos CD20 , Neurologia , Doenças do Sistema Nervoso , Rituximab/efeitos adversos , Estudos Retrospectivos
6.
SAR QSAR Environ Res ; 32(1): 71-83, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33455460

RESUMO

Chagas disease is endemic to 21 Latin American countries and is a great public health problem in that region. Current chemotherapy remains unsatisfactory; consequently the need to search for new drugs persists. Here we present a new approach to identify novel compounds with potential anti-chagasic action. A large dataset of 584 compounds, obtained from the Drugs for Neglected Diseases initiative, was selected to develop the computational model. Dragon software was used to calculate the molecular descriptors and WEKA software to obtain the classification tree. The best model shows accuracy greater than 93.4% for the training set; the tree was also validated using a 10-fold cross-validation procedure and through a test set, achieving accuracy values over 90.5% and 92.2%, correspondingly. The values of sensitivity and specificity were around 90% in all series; also the false alarm rate values were under 10.5% for all sets. In addition, a simulated ligand-based virtual screening for several compounds recently reported as promising anti-chagasic agents was carried out, yielding good agreement between predictions and experimental results. Finally, the present work constitutes an example of how this rational computer-based method can help reduce the cost and increase the rate in which novel compounds are developed against Chagas disease.


Assuntos
Antiprotozoários/farmacologia , Relação Quantitativa Estrutura-Atividade , Trypanosoma cruzi/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Ligantes , Estrutura Molecular , Software
7.
Rev. psicol. deport ; 28(supl.1): 30-34, 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-190218

RESUMO

El objetivo del presente estudio fue conocer cómo influye el modelo deportivo de la Fundación Real Madrid (FRM) en los factores personales y sociales de la deportividad. La muestra de estudio estaba formada por 413 jugadores pertenecientes a las Escuelas Sociodeportivas de Baloncesto de la FRM de la Comunidad de Madrid (281 chicos y 132 chicas) de las categorías benjamín, alevín, infantil y cadete. Se utilizó la Escala Multidimensional de Orientaciones hacia la Deportividad. Entre los principales resultados, se detectaron valores más altos en los factores personales que en los factores sociales. Las chicas mostraron valores más elevados en los factores personales (p < .024). Los deportistas que participaban en las competiciones internas de la FRM presentaron actitudes más deportivas que los que no lo hacían (p < .007). Los jugadores pertenecientes a las categorías más pequeñas mostraron mayor orientación hacia la deportividad. Finalmente, se observó una correlación positiva entre ambas dimensiones (rs = 0.542, p < .001). Los datos mostraron que el modelo deportivo de la FRM contribuye al desarrollo de la deportividad de los jóvenes deportistas


The aim of this study was to know how the sports model of the Real Madrid Foundation (FRM) influences the personal and social factors of sportsmanship. The study sample consisted of 413 players from Social-Sports Basketball Schools of the FRM in the Community of Madrid (281 boys and 132 girls) belonging to U10, U12, U14 y U16 categories. The Multidimensional Scale of Orientations towards Sportsmanship was used. Among the main results, higher values were detected in personal factors than in social factors. The girls showed higher values in personal factors (p < .024). Athletes participating in the FRM's internal competitions had more sporting attitudes than those who did not (p < .007). Players in the smaller categories showed a greater orientation towards sportsmanship. Finally, a positive correlation was observed between both dimensions (rs = 0.542, p < .001). The data showed that the FRM's sports model contributes to the development of sportsmanship among young athletes


O objetivo do presente estudo foi conhecer como o modelo esportivo da Fundação Real Madrid (FRM) influencia os fatores pessoais e sociais do esportivismo. A amostra de estudo foi formada por 413 jogadores pertencentes às Escolas de Basquete Sócio-esportivas da FRM da Comunidade de Madri, 281 meninos e 132 meninas, pertencentes às categorias Benjamin, alevín, infantil e cadete. A Escala de Orientação Multidimensional para o Esportismo foi usada. Entre os principais resultados, valores mais altos foram encontrados em fatores pessoais do que em fatores sociais, e as meninas apresentaram valores mais altos em fatores pessoais (p < .024). Os atletas participantes das competições internas do FRM apresentaram mais atitudes esportivas do que aqueles que não participaram deles (p < .007). Os atletas pertencentes às categorias menores mostraram maior orientação para o espírito esportivo. Finalmente, correlação positiva foi observada entre as duas dimensões (rs = 0.542, p < .001). Os resultados mostraram que o modelo esportivo do FRM contribui para o desenvolvimento do espírito esportivo de jovens atletas


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Esportes Juvenis , Valores Sociais , Basquetebol , Ética Baseada em Princípios
8.
Mar Environ Res ; 130: 166-173, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28760622

RESUMO

Particulate wastes derived from cage fish farming are a trophic resource used by wild fish. This study assesses waste consumption by wild fish and the impact on the final balance of wastes. Consumption was determined according to the difference between the particulate matter exiting the cages and that reaching 5 m away at three different depths, in the presence and absence of wild fish. Wild fish around the experimental cages were counted during feeding and non-feeding periods. A weighted abundance of 1057 fish 1000 m-3 consumed 17.75% of the particulate wastes exiting the cages, on average. Consumption was higher below the cages, where waste outflow was greater. However, waste removal by wild fish was noteworthy along the shallow and deep sides of the cages. Wild fish diminished the net particulate wastes by about 14%, transforming them into more easily dispersible and less harmful wastes. This study demonstrates the mitigating potential of wild fish in reducing environmental impact.


Assuntos
Aquicultura , Peixes , Resíduos Sólidos , Animais , Meio Ambiente , Tamanho da Partícula
10.
Rev Neurol ; 64(10): 445-453, 2017 May 16.
Artigo em Espanhol | MEDLINE | ID: mdl-28497440

RESUMO

INTRODUCTION: Fingolimod is a selective immunosuppressant that targets the S1P receptor, and is indicated in the treatment of aggressive relapsing-remitting multiple sclerosis (RRMS) and following treatment failure with first-order drugs. AIM: To investigate the safety and effectiveness of fingolimod under the conditions of routine clinical practice. PATIENTS AND METHODS: We conducted an observational study with prospective follow-up of patients with RRMS who received fingolimod from January 2011 until February 2014. Data assessed were the annualised relapse rate (ARR), disability measured by the Expanded Disability Status Scale (EDSS), magnetic resonance activity and the appearance of side effects. RESULTS: Our sample consisted of 122 patients, 79.5% of them females and with a mean age of 26.8 years. They were classified, according to the last treatment received, as being: naive (aggressive RRMS; n = 17), previous treatment failure (n = 67) and withdrawal of natalizumab due to risk of progressive multifocal leukoencephalopathy (n = 38). After a mean follow-up of 29.9 ± 15.9 months, the ARR and the appearance of new lesions with gadolinium enhancement were reduced in both the naive and the previous treatment failure groups. There were no differences between the various subgroups as regards the progression of EDSS or the time elapsed until the first attack or treatment failure. The risk of treatment failure is higher with a baseline EDSS > 3 (hazard ratio: 4.24; p = 0.001) and presence of IgM oligoclonal bands (hazard ratio: 2.45; p < 0.022). CONCLUSIONS: Fingolimod is an effective and well-tolerated drug under conditions of routine clinical practice. Having a baseline EDSS > 3 and IgM oligoclonal bands is predictive of a poor response to fingolimod.


TITLE: Tratamiento de la esclerosis multiple remitente recurrente con fingolimod en la practica clinica habitual.Introduccion. El fingolimod es un inmunosupresor selectivo dirigido contra el receptor SP-1, indicado en el tratamiento de la esclerosis multiple remitente recurrente (EMRR) agresiva y tras el fracaso del tratamiento con farmacos de primera linea. Objetivo. Investigar la seguridad y efectividad del fingolimod en condiciones de practica clinica habitual. Pacientes y metodos. Estudio observacional con seguimiento prospectivo de pacientes con EMRR que recibieron fingolimod desde enero de 2011 hasta febrero de 2014. Se evaluo la tasa anual de brotes (TAB), la discapacidad medida por la escala expandida del estado de discapacidad (EDSS), la actividad en la resonancia magnetica y la aparicion de efectos adversos. Resultados. Incluimos 122 pacientes, el 79,5% mujeres y con una edad media de 26,8 antilde;os. Se clasificaron segun el ultimo tratamiento recibido en: naive (EMRR agresiva; n = 17), fracaso a terapias previas (n = 67) y retirada de natalizumab por riesgo de leucoencefalopatia multifocal progresiva (n = 38). Tras un seguimiento medio de 29,9 ± 15,9 meses, se redujo de forma significativa la TAB y la aparicion de nuevas lesiones con realce de gadolinio en el grupo naive y el de fracaso a terapias previas. No ha habido diferencias en la evolucion de la EDSS ni en el tiempo hasta el primer brote o el fracaso terapeutico entre los diferentes subgrupos. El riesgo a fracaso terapeutico es mayor con la EDSS basal > 3 (hazard ratio: 4,24; p = 0,001) y presencia de bandas oligoclonales IgM (hazard ratio: 2,45; p < 0,022). Conclusiones. El fingolimod es un farmaco eficaz y seguro en la EMRR en condiciones de practica clinica habitual. Tener una EDSS basal > 3 y bandas oligoclonales IgM predice una mala respuesta al fingolimod.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Meios de Contraste , Avaliação da Deficiência , Intervalo Livre de Doença , Substituição de Medicamentos , Feminino , Cloridrato de Fingolimode/efeitos adversos , Seguimentos , Gadolínio , Humanos , Imunossupressores/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/patologia , Natalizumab/efeitos adversos , Neuroimagem , Bandas Oligoclonais/líquido cefalorraquidiano , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
11.
Mar Pollut Bull ; 119(1): 23-30, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28325608

RESUMO

Particulate wastes drive benthic organic enrichment from cage fish farming. Differentiation between faeces and uneaten feed estimates at cage level are of great value to both economize the feeding process and reduce waste. This study estimates the particulate waste outflowing cages at different depths and orientations, and the wasted feed component by combining in situ measurements and modelling. Particulate matter flux (PMF) was greater vertically through the cage bottoms (60.89%), but lateral outflow was also substantial (39.11%). PMF occurs all around the cages, and the influence of the mainstream current was low. Wasted feed was greatly variable, reaching high values (about 50% of supplied feed. The self-application of feed wastage monitoring and estimates by fish farmers is recommended to improve sustainability.


Assuntos
Aquicultura , Eliminação de Resíduos , Animais , Peixes , Tamanho da Partícula
13.
Mar Environ Res ; 122: 46-58, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27686388

RESUMO

Cage aquaculture aggregates wild fauna due to food provision. Several seabirds frequent fish farms, including the European storm-petrel (Hydrobates pelagicus melitensis). This work investigates the presence of storm-petrels around two aquaculture areas interspersed between breeding colonies in western Mediterranean Sea. Contribution of aquaculture-derived resources to their diet was assessed. Storm-petrels were mist-netted at the colonies and marked by bleaching feathers. Density around aquaculture areas was estimated through visual counts. Marks recognition was conducted visually and by photo-capture. Storm-petrel regurgitates were used as target tissue to estimate diet sources contribution. Contribution of surface zooplankton, ichthyoplankton and aquaculture wastes was estimated through Bayesian mixing modelling combining carbon and nitrogen stable isotopes and fatty acids as biomarkers. Storm-petrel density was high in open-sea aquaculture area, but not observed around near shore farms. Temporal variability of storm-petrels density during the breeding season was linked to their reproductive phenology. Within the open-sea aquaculture area, bluefin tuna farm was more attractive for storm-petrels than seabream/seabass farms. Visual identification of bleaching marks was not useful. Photo-capture showed that 8.3% of the storm-petrels watched around farms were firstly trapped in some of the nearby colonies, and 91.7% were unmarked. Qualitative evidence of aquaculture-derived wastes utilization was obtained. However, its estimated contribution was low (4.3%) when compared to ichthyoplankton (61.1%) or zooplankton (34.6%). The studied open-sea farms significantly aggregated storm-petrels along their entire breeding season. Storm-petrels got a slight profit from aquaculture resources. Nevertheless, some concerns arise regarding the cost/benefit balance of the interaction.


Assuntos
Aquicultura/estatística & dados numéricos , Aves/fisiologia , Animais , Aquicultura/métodos , Teorema de Bayes , Análise Custo-Benefício , Mar Mediterrâneo
14.
SAR QSAR Environ Res ; 26(11): 943-58, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26567876

RESUMO

The QuBiLs-MAS approach is used for the in silico modelling of the antifungal activity of organic molecules. To this effect, non-stochastic (NS) and simple-stochastic (SS) atom-based quadratic indices are used to codify chemical information for a comprehensive dataset of 2478 compounds having a great structural variability, with 1087 of them being antifungal agents, covering the broadest antifungal mechanisms of action known so far. The NS and SS index-based antifungal activity classification models obtained using linear discriminant analysis (LDA) yield correct classification percentages of 90.73% and 92.47%, respectively, for the training set. Additionally, these models are able to correctly classify 92.16% and 87.56% of 706 compounds in an external test set. A comparison of the statistical parameters of the QuBiLs-MAS LDA-based models with those for models reported in the literature reveals comparable to superior performance, although the latter were built over much smaller and less diverse datasets, representing fewer mechanisms of action. It may therefore be inferred that the QuBiLs-MAS method constitutes a valuable tool useful in the design and/or selection of new and broad spectrum agents against life-threatening fungal infections.


Assuntos
Antifúngicos/química , Relação Quantitativa Estrutura-Atividade , Simulação por Computador , Análise Discriminante , Descoberta de Drogas , Modelos Lineares
15.
Haemophilia ; 21(4): 458-64, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25649244

RESUMO

Treatment adherence in adolescents with chronic diseases is around 50%, and failure is more common in preventive therapy. In haemophilia, contradictory results are reported by the published studies. The objective of this study was to evaluate adherence with factor VIII (FVIII) prophylaxis in Spanish patients with severe haemophilia A between age 6 and 20 years. Data were collected retrosp-ectively in the previous 2 years. The primary endpoint was the absolute adherence index (AAI), and the endpoints were related to clinical status, age, prophylaxis regimen, responsibility for factor administration and quality of life (QoL), assessed by the Haemo-QoL questionnaires. A total of 78 patients from 14 Spanish hospitals were recruited. Adherence ranged between -64.4 and 66.7 (mean -3.08). No differences were observed between children and adolescents (7.11 vs. 6.39; P = 0.809). A statistically significant association (P < 0.010) between infra adherent group and target joint was found, as was a statistically significant difference (P < 0.010) between the number of bleeding episodes experienced by the adherent group (mean 1.4) and by infra adherents (mean 4.5). There was no significant difference between AAI and prophylactic regimen (6.35 vs. 6.96, P = 0.848), neither between AAI and the person responsible for factor administration (5.57 vs. 8.79, P = 0.326). The Haemo-QoL scores (8-12 years) were related to adherence level (P < 0.05). Adherence was approximately ideal and patients perceived a high QoL. Because of the repercussions for compliance, it is essential to work during puberty on emotional and self-acceptance aspects of the disease, as well as coping, and the patient's family, school and health team relationships.


Assuntos
Hemofilia A/psicologia , Cooperação do Paciente , Qualidade de Vida , Adolescente , Criança , Estudos Transversais , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia A/patologia , Humanos , Masculino , Pais/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
16.
Mar Environ Res ; 103: 27-35, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25460059

RESUMO

"Taxocene surrogation" and "taxonomic sufficiency" concepts were applied to the monitoring of soft bottoms macrobenthic assemblages influenced by fish farming following two approaches. Polychaete assemblage evaluation through multivariate analysis and the benthic index BOPA were compared. Six fish farms along the Spanish Mediterranean coast were monitored. Polychaete assemblage provided a suitable picture of the impact gradient, being correlated with total free sulphides. BOPA did not support the impact gradient described by the polychaete assemblage, providing erroneous categorizations. The inclusion of several polychaete families, which were locally identified as indicative of affection to recalculate BOPA, resulted in an improved diagnosis and correlation with the impact gradient. Nevertheless, frequent misclassifications occurred. These results suggest that the structure of polychaete families, sulphides and granulometry conform an appropriate strategy for fish farming monitoring. Biotic indices need to be specifically designed for concrete activities, and regionally validated, because of the environmental plasticity of benthic invertebrates.


Assuntos
Aquicultura , Biodiversidade , Monitoramento Ambiental/métodos , Poliquetos/fisiologia , Sulfetos/análise , Anfípodes/fisiologia , Animais , Organismos Aquáticos/fisiologia , Bass/fisiologia , Sedimentos Geológicos/análise , Mar Mediterrâneo , Análise Multivariada , Dourada/fisiologia , Espanha
17.
Res Vet Sci ; 94(1): 9-21, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22884173

RESUMO

Spoligotyping is the most frequently used method for genotyping isolates of Mycobacterium bovis worldwide. In the current work, we compared spoligotypes from 1684 M. bovis isolates from Argentina (816), Brazil (412), Chile (66), Mexico (274) and Venezuela (116), obtained from cattle, humans, pigs, wild boars, farmed deer, goats, buffaloes, cats, and wild animals. A total of 269 different spoligotypes were found: 142 (8.4%) isolates presented orphan spoligotypes, whereas 1542 (91.6%) formed 113 different clusters. In cattle, SB0140 was the most representative spoligotype with 355 (24.6%) isolates, followed by SB0121 with 149 (10.3%) isolates. Clustering of spoligotypes ranged from 95.2% in Argentina to 85.3% in Mexico. Orphan spoligotypes were also variable, ranging from 23.7% in Mexico to 4.1% in Brazil. A large proportion of spoligotypes were common to the neighboring countries Argentina, Brazil and Chile. In conclusion, despite the diversity of spoligotypes found in the five countries studied, there are major patterns that predominate in these neighboring countries. These clusters may reflect a long-lasting active transmission of bovine tuberculosis or common historical origins of infection.


Assuntos
Mycobacterium bovis/genética , Tuberculose Bovina/microbiologia , Animais , Animais Selvagens/microbiologia , Argentina , Brasil , Búfalos/microbiologia , Gatos/microbiologia , Bovinos/microbiologia , Humanos , México , Tipagem Molecular/veterinária , Sus scrofa/microbiologia , Suínos/microbiologia , Tuberculose/veterinária , Venezuela
18.
Theriogenology ; 78(5): 1056-64, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22704391

RESUMO

The aim was to design a protocol combining eCG followed by hCG for estrus induction in the bitch. In Experiment 1, three ovariohysterectomized bitches received 10 000 IU of eCG iv, and 15 days later 10 000 IU of eCG im. Blood samples were taken up to 144 h after each injection to measure eCG concentrations. In Experiment 2, 25 healthy, intact late anestrous bitches were assigned to one of five doses of eCG (5, 10, 15, 20, 44, or 50 IU/kg eCG im; [TRT5-TRT50]). Sexual behavior (SB), clinical signs of estrus (CSE) and vaginal cytology (VC) samples were obtained and scored before eCG administration and every other day until onset of estrus, or for 14 days. In Experiment 3, intact late anestrous bitches were assigned to a treatment group (TRT; n = 16) and received eCG (50 IU/kg im) followed by hCG (500 IU im) 7 days later; or to a placebo group (PLA; n = 8) where they received 1 mL saline solution im. All bitches that were induced in estrus were mated or AI with fresh semen. In Experiment 1, maximum observed concentration (C(max)) eCG were similar between im and iv routes (6.1 ± 0.9 vs. 8.6 ± 0.5 IU/mL, P > 0.08), whereas time for maximum observed concentration (T(max.)) was longer for im compared to iv routes (17.5 ± 0.5 vs. 11.6 ± 0.3 h, P < 0.01). The area under the curve (AUC) was similar for im and iv routes (P > 0.48), and eCG was detectable in serum for at least 144 h for both routes. In Experiment 2, 3 days or 3 to 5 days after treatment, all bitches in TRT50 had higher scores compared to TRT5-44 animals (P < 0.01). In TRT50, the mean interval from treatment to estrus was 4.0 ± 0.4 days. In Experiment 3, the mean interval from treatment to estrus was shorter in the TRT group compared to the PLA group (4.1 ± 3.3 vs. 68.5 ± 4.4 days, P < 0.01). The previous interestrus interval was similar for TRT and PLA groups (199.6 ± 7.2 vs. 197.5 ± 10.2 days), but the new interestrus interval was shorter for the TRT compared to the PLA group (164.0 ± 7.2 vs. 212.2 ± 10.2 days; treatment by interval interaction, P < 0.007). Serum P(4) concentrations increased on the first day of cytologic diestrus after treatment in bitches in TRT (0.7 ± 0.3 vs. 22.8 ± 4.2 ng/mL; P < 0.01); but did not change in PLA (P > 0.84). Ninety-four percent of animals were bred (15/16; AI, n = 7; natural mating, n = 8), and 80% (12/15) became pregnant. None of the bitches had any side effects from the eCG and hCG therapy. We concluded that 50 IU/kg of eCG combined 7 days later with 500 IU of hCG was effective to induce normal and fertile estrus in bitches at 164 days post estrus, with an 80% pregnancy rate, with no side effects, and with a reduction of 48 days of the interestrus interval.


Assuntos
Gonadotropina Coriônica/farmacologia , Gonadotropina Coriônica/farmacocinética , Estro/efeitos dos fármacos , Animais , Área Sob a Curva , Gonadotropina Coriônica/administração & dosagem , Cães , Vias de Administração de Medicamentos , Feminino , Meia-Vida , Cavalos , Humanos , Masculino , Gravidez , Comportamento Sexual Animal
19.
Mar Pollut Bull ; 64(4): 729-38, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22386801

RESUMO

The development of a benthic environment after fish-farming cessation was examined. To ascertain whether recovery occurred, several abiotic (granulometry, acid-volatile sulfides, total phosphorus and redox potential) and biotic (polychaete abundance) variables were monitored using a "beyond-BACI" approach. Before the cessation of farming, the geochemical conditions and polychaete assemblages differed among the impacted and control sites. After cessation, an improvement of the geochemical conditions was achieved. A significant tendency toward a recovery of the polychaete assemblage in the impacted area was observed, but significant differences still remained compared with the control sites. The acid-volatile sulfide level was responsible for these differences. The abundance of polychaete families associated with organically enriched sediments diminished at the impacted site after cessation, whereas the abundance of some sensitive and omnivorous families increased. The "beyond-BACI" approach provided a wider framework than other approaches, enabling us to differentiate the natural variability from those changes induced by the fish farm and farming cessation.


Assuntos
Ecossistema , Monitoramento Ambiental , Pesqueiros , Sedimentos Geológicos/análise , Sedimentos Geológicos/química , Poliquetos/fisiologia , Animais , Água do Mar/análise
20.
Mar Environ Res ; 74: 47-55, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22209704

RESUMO

This work concerns the monitoring of a Mediterranean maërl bed influenced by an experimental fish cage culture for eighteen months. The maërl bed showed an a priori stratified distribution with depth, which led to the selection of a stratified random sampling design that also took into account the gradient of influence by the fish cages. Maërl coverage and total biomass, macroalgae species richness and community structure as determined from semi-quantitative abundance data were assessed. The content of organic matter sediment was also considered. Sampling campaigns (performed by scuba divers) were carried out six months before the start of the culture, twice during the culture, and two months after the end of the experimental culture. Below the fish cages, the maërl community was almost completely buried and dead blackened calcareous algae were seen beneath a thin layer of sediment prior to the end of the study, and only a few specimens of Lithophyllum racemus, Flabellia petiolata, Gracilaria cylindrica and Meredithia microphylla remained alive. The influence of the experimental culture on the maërl algae community structure bed did not extend beyond the facilities, but a regression of the community was also observed close to the fish cages. Sensitivity to aquaculture activity, and the ecological benefits provided by maërl beds suggest that this community warrants further consideration when planning fish farm site selection and management.


Assuntos
Monitoramento Ambiental , Peixes , Rodófitas/crescimento & desenvolvimento , Animais , Aquicultura , Ecossistema , Mar Mediterrâneo , Água do Mar , Espanha , Movimentos da Água , Poluição da Água/prevenção & controle
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