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1.
J Dairy Sci ; 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38135046

ABSTRACT

Pedigrees used in genetic evaluations contain errors. Because of such errors, assumptions regarding the relatedness among individuals in genetic evaluation models are wrong. Consequences of that have been investigated in earlier studies focusing on models that did not account for genomic information yet. The objective of this work was to investigate the effects of pedigree errors on the results from genetic evaluations using the single-step model, and the impact of such effects on results from validation studies with forward prediction. We used a real pedigree (n = 361,980) and real genotypes (n = 25,950) of Fleckvieh cattle, sampled in a way to provide a good consistency between pedigree and genomic relationships. Given the real pedigree and genotypes, true breeding values were simulated to have a covariance structure equal to the matrix H assumed in a single-step model. Based on true breeding values, phenotypes were simulated with a heritability of 0.25. Genetic evaluations were conducted with a conventional animal model (i.e., without genomic information) and a single-step animal model under scenarios using either the correct pedigree or a pedigree containing 5, 10 or 20% of wrong records. Wrong records were simulated by randomly assigning wrong sires to non-genotyped females. The increasing rates of pedigree errors led to decreasing correlations between true and estimated breeding values and lower standard deviations of predictions. Less variation was observed because pedigree errors operate actually as a random exchange of daughters among bulls, making them look more similar to each other than they actually are. This occurs of course only when animals have progeny. Therefore, this decreased variation was more pronounced for progeny tested bulls than for young selection candidates. In a forward prediction validation scenario, the stronger decrease in variation when animals get progeny caused an apparent inflation of early predictions. This phenomenon may contribute to the usually observed problem of inflation of early predictions observed in validation studies.

2.
Environ Toxicol Pharmacol ; 80: 103464, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32750419

ABSTRACT

The identification of substances that prevent or minimize the detrimental effects of ionizing radiation is an essential undertaking. The aim of this paper was to evaluate and compare the radioprotective potential of chlorophyllin, protoporphyrin and bilirubin, with amifostine®, an US Food & Drug Administration approved radioprotector Using the somatic mutation and recombination assay in the Drosophila melanogaster wing, it was found that pretreatment (1-9 h) with any of the porphyrins or amifostine® alone, did not affect the larva-adult viability or the basal frequency of mutation. However, they were associated with significant reductions in frequency of somatic mutation and recombination compared with the gamma-irradiated (20 Gy) control as follows: bilirubin (69.3 %)> chlorophyllin (40.0 %)> protoporphyrin (39.0 %)> amifostine® (19.7 %). Bilirubin also caused a 16 % increase in larva-adult viability with 3 h of pretreatment respect to percentage induced in 20 Gy control group. Whilst amifostine® was associated with lower genetic damage after pre-treatment of 1 and 3 h, this did not attain significance. These findings suggest that the tested porphyrins may have some potential as radioprotectant agents.


Subject(s)
Amifostine/pharmacology , Bilirubin/pharmacology , Chlorophyllides/pharmacology , Drosophila melanogaster/drug effects , Drosophila melanogaster/radiation effects , Protoporphyrins/pharmacology , Radiation-Protective Agents/pharmacology , Animals , Drosophila melanogaster/genetics , Female , Male , Mutagenicity Tests , Mutation/drug effects , Recombination, Genetic/drug effects , Wings, Animal/drug effects , Wings, Animal/radiation effects
3.
Serv. soc. soc ; (134): 34-51, jan.-abr. 2019.
Article in Portuguese | LILACS | ID: biblio-986107

ABSTRACT

Resumo: O objetivo deste estudo foi discutir o método materialista histórico dialético, apontando elementos essenciais presentes no percurso metodológico. O método em Marx é um movimento dialético que parte da sua concepção ontológica da realidade social, em que o ser social produz suas próprias condições objetivas e subjetivas de existência e, por isso, teoria, método e concreto social constituem uma unidade metodológica.


Abstract: The objective of this study was to discuss the dialectical historical materialist method, pointing out essential elements present in the methodological course. The method in Marx is a dialectical movement that starts from its ontological conception of social reality, in which the social being produces its own objective and subjective conditions of existence and, therefore, theory, method and social concrete constitute a methodological unit.

4.
J Dairy Sci ; 102(4): 3266-3273, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30799116

ABSTRACT

Single-step genomic evaluations have the advantage of simultaneously combining all pedigree, phenotypic, and genotypic information available. However, systems with a large number of genotyped animals have some computational challenges. In many genomic breeding programs, genomic predictions of young animals should become available for selection decisions in the shortest time possible, which requires either a very effective estimation or an approximation with negligible loss in accuracy. We investigated different procedures for predicting breeding values of young genotyped animals without setting up the full single-step system augmented for the additional genotypes. Methods were based on transmitting the information from single-step breeding values of genotyped animals that took part in the previous full run to young animals, either through genomic relationships or through a marker-based model. The different procedures were tested on real data from the April 2017 run of the German-Austrian official genomic evaluation for Fleckvieh. The data set included 62,559 genotyped animals and was used to run single-step evaluations for 23 conformation traits. A further data set comprising 1,768 young animals was used for interim prediction and we called it the validation set. The reference values for validation were the predicted breeding values of the young animals from a full single-step run containing the genotypes of all 64,327 animals. Correlations between the approximated predictions and those from the full single-step run also containing genotypes from young animals averaged 0.9932 for the best method (from 0.990 to 0.995 across traits). In conclusion, prediction of single-step breeding values for young animals can be well approximated using systems of size equal to the number of markers.


Subject(s)
Breeding , Cattle , Genomics , Models, Genetic , Animals , Austria , Genotype , Pedigree , Phenotype , Polymorphism, Single Nucleotide
5.
J Dairy Sci ; 102(4): 3259-3265, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30738687

ABSTRACT

It has been shown that single-step genomic BLUP (ssGBLUP) can be reformulated, resulting in an equivalent SNP model that includes the explicit imputation of gene contents of all ungenotyped animals in the pedigree. This reformulation reveals the underlying mechanism enabling ungenotyped animals to contribute information to genotyped animals via estimates of marker effects and consequently to the reliability of genomic predictions, a key feature generally associated with the single-step approach. Irrespective of which BLUP formulation is used for genomic prediction, with increasing numbers of genotyped animals, the marker-oriented model is recommended when calculating the reliabilities of genomic predictions. This approach has the advantage of a manageable and stable size of the model matrix that needs to be inverted to calculate analytical prediction error variances of marker effects, an advantage that also holds for prediction with the single-step model. However, when including imputed genotypes in the design matrix of marker effects, an additional imputation residual term has to be considered to account for the prediction error of imputation. We summarize some of the theoretical aspects associated with the calculation of analytical reliabilities of single-step predictions. Derivations are based on the equivalent reformulation of ssGBLUP as a marker-oriented model and the calculation of prediction error variances of marker effects. We propose 2 approximations that allow for a substantial reduction of the complexity of the matrix operations involved, while retaining most of the relevant information required for reliability calculations. We additionally provide a general framework for an implementation of single-step reliability approximation using standard animal model reliabilities as a starting point. Finally, we demonstrate the effectiveness of the proposed approach using a small example extracted from data of the routine evaluation on dual-purpose Fleckvieh (Simmental) cattle.


Subject(s)
Cattle/genetics , Genomics , Models, Genetic , Animals , Breeding , Genome , Pedigree , Phenotype , Polymorphism, Single Nucleotide , Reproducibility of Results
6.
Hernia ; 23(1): 119-123, 2019 02.
Article in English | MEDLINE | ID: mdl-30259218

ABSTRACT

BACKGROUND: Cholecystectomy and inguinal hernioplasty are the most frequent surgeries in Chile and the world. Laparoscopic inguinal hernioplasty, being a clean surgery, reports mesh infection rates of less than 2% and adding a simultaneous laparoscopic cholecystectomy is controversial due to an increase in the risk of mesh infection. The aim of this paper is to report the results of simultaneous TAPP hernioplasty with laparoscopic cholecystectomy. METHOD: Retrospective analysis of the digestive surgery database. We identified cases in which laparoscopic inguinal TAPP repair and simultaneous laparoscopic cholecystectomy were performed. Demographic, clinical information, hernia type and size, data from the surgery and its complications were also retrieved and analyzed. RESULTS: We identified 21 patients, 86% male and with an average age of 61 years range 46-84. 72% of the hernias were unilateral, predominating indirect 50%, direct 28% and the remaining were femoral and mixed. The average hernia size was 2.2 cm. The meshes used were 56% polypropylene, 37% polyester and 5% PVDF. We report one gallblader perforation. At a median time of 40 months of follow-up (range 4-89 months), one hernia recurrence was found (3.7%), there were no reoperations at the time of the interview and there were no cases of mesh infection. Complications of surgery includes one ipsilateral testicular atrophy 4.8% and 1 ipsilateral inguinal seroma 4.8%. CONCLUSIONS: In this series of cases, adding clean contaminated surgery to the inguinal TAPP hernioplasty was not associated with an increase in the infection of the mesh.


Subject(s)
Cholecystectomy, Laparoscopic/methods , Cholelithiasis/surgery , Hernia, Inguinal/surgery , Herniorrhaphy/methods , Adult , Aged , Aged, 80 and over , Cholelithiasis/complications , Female , Follow-Up Studies , Hernia, Inguinal/complications , Humans , Laparoscopy/methods , Male , Middle Aged , Retrospective Studies , Surgical Mesh , Treatment Outcome
7.
Environ Toxicol Pharmacol ; 63: 16-20, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30121516

ABSTRACT

Ionizing radiation plays a key role in the adaptation of an individual organism to environmental pollution, at the same time, it has biological effects that depend on radiation intensity or dose rate (DR). Although the effect of DR has been studied in vitro, the phenomenon known as the inverse effect of DR, which indicates as it decreases that the induction of damage is greater, has not been widely studied in vivo. The present study is aimed to test 0.5 and 1 Gy in somatic cells of the wing of D. melanogaster, administered at 5.4 or 34.3 Gy/h and from 0.037 to 0.3 mM of CrO3 as conditioning treatment. No changes were found in larva-to-adult viability. A protective as well as a cross effect of pre-exposure to different DR and CrO3 concentrations against genetic damage induced by 20 Gy or 1 mM CrO3 was evident.


Subject(s)
Chromium Compounds/pharmacology , Drosophila melanogaster/genetics , Wings, Animal/cytology , Animals , Culture Media, Conditioned , DNA Damage/drug effects , Dose-Response Relationship, Radiation , Drosophila melanogaster/drug effects , Drosophila melanogaster/radiation effects , Female , Radiation Tolerance , Radiation, Ionizing , Wings, Animal/drug effects , Wings, Animal/radiation effects
8.
J Anim Breed Genet ; 135(3): 151-158, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29582470

ABSTRACT

Single-step models including dominance can be an enormous computational task and can even be prohibitive for practical application. In this study, we try to answer the question whether a reduced single-step model is able to estimate breeding values of bulls and breeding values, dominance deviations and total genetic values of cows with acceptable quality. Genetic values and phenotypes were simulated (500 repetitions) for a small Fleckvieh pedigree consisting of 371 bulls (180 thereof genotyped) and 553 cows (40 thereof genotyped). This pedigree was virtually extended for 2,407 non-genotyped daughters. Genetic values were estimated with the single-step model and with different reduced single-step models. Including more relatives of genotyped cows in the reduced single-step model resulted in a better agreement of results with the single-step model. Accuracies of genetic values were largest with single-step and smallest with reduced single-step when only the cows genotyped were modelled. The results indicate that a reduced single-step model is suitable to estimate breeding values of bulls and breeding values, dominance deviations and total genetic values of cows with acceptable quality.


Subject(s)
Breeding , Cattle/genetics , Genomics/methods , Models, Genetic , Social Dominance , Animals , Cattle/physiology , Female , Genotype , Male , Pedigree , Phenotype
9.
Medwave ; 18(1): e7159, 2018.
Article in English, Spanish | LILACS | ID: biblio-908971

ABSTRACT

Las benzodiacepinas son fármacos ampliamente utilizados en atención primaria de salud. Su uso prolongado se ha convertido en un problema relevante dadas las consecuencias médicas que ocasionan, especialmente en adultos mayores. Entre otras, estas son: dependencia, deterioro cognitivo y riesgo de caídas. Además, los médicos que trabajan en atención primaria cuentan con pocas herramientas para ayudar al paciente en su deshabituación. Se realizó una búsqueda y revisión de la mejor evidencia disponible sobre estrategias prácticas para el médico no especialista en adicciones, para evitar la dependencia al momento de la prescripción inicial y en el paciente con uso prolongado y probablemente dependiente. Se encontraron 10 revisiones sistemáticas relevantes que mostraron evidencia a favor del uso de estrategias multifacéticas en la prescripción, disminución progresiva, cartas y consejería estandarizadas, farmacoterapia y psicoterapia cognitiva conductual. Una estrategia sencilla, eficaz y duradera para prescribir benzodiacepinas es informar al paciente de la necesidad de reducir su consumo, dándole por escrito la pauta de retirada, señalando sus posibles efectos y su solución. Debido a la evidencia disponible, se propone un modelo integrado y escalonado para el manejo del paciente usuario de benzodiacepinas, desde su prescripción hasta su descontinuación.


Benzodiazepines are widely used in primary health care, and their prolonged use is an important problem given the medical consequences particularly in older adults, such as dependence, cognitive impairment, and risk of falls, among others. Primary care doctors generally have few tools to help with managing withdrawal from benzodiazepines. We conducted a review of the best available evidence on practical strategies to avoid dependence at the time of the initial prescription, and to help the patient with prolonged and probably dependent use. We found ten relevant systematic reviews showing evidence in favor of the use of multifaceted prescription strategies, gradual dose reduction, standardized letters, standardized counseling, pharmacotherapy and cognitive behavioral psychotherapy. For benzodiazepine withdrawal, a simple strategy that can be effective and long-lasting is to inform patients of the need to reduce consumption, giving them in writing the withdrawal guideline, indicating the possible effects of withdrawal and its solution. Given the available evidence, an integrated and step-by-step model is proposed for the management of the benzodiazepine user, from prescription to withdrawal.


Subject(s)
Humans , Aged , Substance Withdrawal Syndrome/therapy , Benzodiazepines/adverse effects , Substance-Related Disorders/rehabilitation , Primary Health Care/methods , Anti-Anxiety Agents/administration & dosage , Anti-Anxiety Agents/adverse effects , Benzodiazepines/administration & dosage
10.
Medwave ; 18(1): e7138, 2018.
Article in English, Spanish | LILACS | ID: biblio-909780

ABSTRACT

INTRODUCCIÓN: La trabeculectomía es considerada la intervención de elección en pacientes con glaucoma con indicación de manejo quirúrgico. Dentro de los factores asociados al fracaso de este tratamiento se encuentra la cicatrización postoperatoria. Para disminuir este factor se han usado distintos antimetabolitos, en particular el 5-fluorouracilo y la mitomicina C. Si bien ambos se consideran efectivos, no está claro si existen diferencias entre ambos en relación al éxito de la trabeculectomía y los efectos adversos. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, preparamos tablas de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cuatro revisiones sistemáticas que en conjunto incluyen 17 estudios primarios, de los cuales, 12 corresponden a ensayos aleatorizados. Concluimos que el uso de mitomicina C podría lograr una mayor disminución de la presión intraocular e incrementar la tasa de éxito calificado en comparación con el 5-fluorouracilo. Sin embargo, su uso podría asociarse a una mayor incidencia de complicaciones.


INTRODUCTION: Trabeculectomy is considered the standard for glaucoma surgery. Postoperative scarring is one the factors associated with surgery failure. Different antimetabolites have been used in order to reduce this risk, particularly 5-fluorouracil and mitomycin C. Although both are considered effective, it is not clear if they are different in terms of success of trabeculectomy and adverse effects. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified four systematic reviews including 17 studies overall, of which 12 were randomized trials. We concluded mitomycin C might be more effective in reducing intraocular pressure and increasing qualified success compared to 5-fluorouracil. However, its use might be associated to a higher risk of complications.


Subject(s)
Humans , Trabeculectomy/methods , Glaucoma/surgery , Mitomycin/administration & dosage , Fluorouracil/administration & dosage , Randomized Controlled Trials as Topic , Cicatrix/prevention & control , Intraocular Pressure , Antimetabolites/administration & dosage
11.
Medwave ; 18(5): e7238, 2018.
Article in English, Spanish | LILACS | ID: biblio-915409

ABSTRACT

Resumen INTRODUCCIÓN: La derivación acuosa ha surgido como una técnica alternativa a la trabeculectomía, considerada la cirugía de elección en pacientes con glaucoma. Actualmente, se considera que la principal indicación de esta técnica es ante el fracaso de la trabeculectomía o en tipos de glaucoma que tienen alto riesgo de fracasar. La válvula Ahmed y el implante Baerveldt son las derivaciones acuosas más utilizadas. Sin embargo, no está claro cuáles son las diferencias entre estas dos alternativas. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud a nivel mundial, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cinco revisiones sistemáticas que en conjunto incluyeron 10 estudios primarios, de los cuales dos son ensayos aleatorizados. Concluimos que la válvula Ahmed probablemente logra una menor disminución de la presión intraocular; podría lograr un menor éxito calificado y probablemente necesita más reintervenciones que el implante Baerveldt. Respecto al perfil de seguridad, la válvula Ahmed no se presenta claramente superior ni inferior al implante Baerveldt.


Abstract INTRODUCTION: Aqueous shunt has emerged as an alternative technique to trabeculectomy, considered the standard for glaucoma surgery. Currently, it is mainly indicated after failure of trabeculectomy or in glaucoma with high risk of failure. The Ahmed valve and the Baerveldt implant are the most commonly used aqueous shunts. However, it is not clear whether there are differences between them. METHODS.: o answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified five systematic reviews including 10 studies overall, of which two were randomized trials. We concluded the Ahmed valve probably achieves a lower decrease in intraocular pressure, might lead to less qualified success and probably needs more reinterventions than the Baerveldt implant. Regarding safety profile, the Ahmed valve is not clearly superior or inferior to the Baerveldt implant.


Subject(s)
Humans , Trabeculectomy/methods , Glaucoma/surgery , Glaucoma Drainage Implants , Trabeculectomy/instrumentation , Randomized Controlled Trials as Topic , Databases, Factual , Treatment Outcome , Prosthesis Implantation/methods , Intraocular Pressure
12.
Medwave ; 18(8): e7389, 2018.
Article in English, Spanish | LILACS | ID: biblio-969324

ABSTRACT

INTRODUCCIÓN: La derivación acuosa ha surgido como una técnica alternativa a la trabeculectomía, la cual se considera el tratamiento estándar para cirugía de glaucoma. Actualmente, su principal indicación es en el glaucoma con trabeculectomía fallida o en algunos tipos de glaucoma con alto riesgo de fracaso. Sin embargo, aún existe controversia con respecto a su efectividad en comparación con la trabeculectomía. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cinco revisiones sistemáticas que en conjunto incluyeron nueve estudios primarios, de los cuales, cuatro corresponden a ensayos aleatorizados. Concluimos que la derivación acuosa podría aumentar el éxito calificado en comparación con la trabeculectomía, pero que no está claro si tiene algún efecto sobre el resto de los desenlaces críticos para la toma de decisión, porque la certeza de la evidencia es muy baja.


INTRODUCTION: Aqueous shunt has emerged as an alternative technique to trabeculectomy, which is considered the standard treatment for glaucoma surgery. Currently, it is mainly indicated after failure of trabeculectomy or in some types of glaucoma with high risk of failure. However, there is still controversy regarding its effectiveness compared to trabeculectomy. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified five systematic reviews including nine studies overall, of which four were randomized trials. We concluded that aqueous shunt might increase the qualified success compared to trabeculectomy, but it is not clear whether it has any effect on the rest of the critical outcomes for decision-making because the certainty of the evidence is very low.


Subject(s)
Humans , Trabeculectomy/methods , Glaucoma/surgery , Glaucoma Drainage Implants , Randomized Controlled Trials as Topic , Databases, Factual , Treatment Outcome
13.
J Dairy Sci ; 100(10): 8277-8281, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28780113

ABSTRACT

In a 2-step genomic system, genotypes of animals without phenotypes do not influence genomic prediction of other animals, but that might not be the case in single-step systems. We investigated the effects of including genotypes from culled bulls on the reliability of genomic predictions from single-step evaluations. Four scenarios with a constant amount of phenotypic information and increasing numbers of genotypes from culled bulls were simulated and compared with respect to prediction reliability. With increasing numbers of genotyped culled bulls, there was a corresponding increase in prediction reliability. For instance, in our simulation scenario the reliability for selection candidates was twice as large when all culled bulls from the last 4 generations were included in the analysis. Single-step evaluations imply the imputation of all nongenotyped animals in the pedigree. We showed that this imputation was increasingly more accurate as increasingly more genotypic information from the culled bulls was taken into account. This resulted in higher prediction reliabilities. The extent of the benefit from including genotypes from culled bulls might be more relevant for small populations with low levels of reliabilities.


Subject(s)
Genomics/methods , Genotype , Phenotype , Animal Culling , Animals , Breeding , Cattle , Male , Models, Genetic , Reproducibility of Results
14.
J Toxicol Environ Health A ; 80(6): 365-373, 2017.
Article in English | MEDLINE | ID: mdl-28644726

ABSTRACT

Casiopeinas® are a group of newly synthesized drugs designed to treat cancer. These copper (Cu) complexes exhibit cytostatic, cytotoxic, genotoxic, and antineoplastic activities through different mechanisms of action. To evaluate the influence of these compounds, some in vivo studies were performed using predominantly somatic cells. The aim of the present study was to examine the cytotoxic and genotoxic actions of Casiopeina III-Ea (Cas III-Ea) in somatic as well as germ cells of Drosophila melanogaster. For cytotoxicity, the productivity and some morphometric parameters were measured and genotoxicity was assessed by means of the somatic mutation and recombination test assay in the wing. For this purpose, second-instar larvae of the Canton-S strain were treated with different concentrations of Cas III-Ea. The emerged adults were weighed, the area of the wings determined, and the number of trichomes of the region C' counted. The productivity of treated males was measured by a brood method to monitor the influence of Cas III-Ea on spermatozoa, meiotic stage cells, and spermatogonia. For genotoxicity, mwh + /+ flr3 larvae 48 hr age were chronically treated within the same concentration range. Results indicated that Cas III-Ea at all concentrations tested significantly increased the productivity per couple in Brood III (spermatids) while at 1 mM a marked elevation was noted in the three broods tested. In contrast, the weight and size of individuals as well as the size and number of cells in the wing were decreased significantly. Data suggest that Cas III-Ea is a weak genotoxic but selective mutagen. Failure to obtain a dose-related genotoxic response suggests that one of the preferred mechanisms of action of Cas III-Ea is to induce apoptosis.


Subject(s)
Antineoplastic Agents/toxicity , Coordination Complexes/toxicity , Phenanthrolines/toxicity , Animals , Drosophila melanogaster/drug effects , Female , Germ Cells/drug effects , Male , Mutagenicity Tests , Wings, Animal/drug effects
15.
Can J Physiol Pharmacol ; 95(4): 333-339, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28112540

ABSTRACT

Over the past few years, a number of cases of tendon injuries associated with statin therapy have been reported. In this study, we assessed whether statins can affect the extracellular matrix (ECM) of the deep digital flexor tendon (DDFT) and patellar tendon (PT). Wistar rats were assigned to groups treated with atorvastatin (A20, A80), treated with simvastatin (S20, S80), and control. Zymography, Western blotting for collagen I, non-collagenous proteins (NCP), glycosaminoglycans (GAGs), and hydroxyproline quantifications were performed. DDFT findings: NCP were increased in A20 and A80; higher concentration of hydroxyproline was found in S80; levels of GAGs was increased in all statin-treated groups; collagen I was increased in S80 and pro-MMP-2 activity was reduced in A80, S20, and S80. PT findings: NCP were reduced in A20, A80, and S80; GAGs was reduced in A80 and S20; collagen I was increased in A20 and pro-MMP-2 activity was reduced in the S20. Both the statins provoked marked changes in both tendons. All these changes may make the tendons more prone to microdamage and ruptures. Therefore, a better understanding of the behavior of the tendon ECM components under statin therapy may provide important insights into the mechanisms behind statin-induced tendon injuries.


Subject(s)
Atorvastatin/adverse effects , Extracellular Matrix/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hyperlipidemias/drug therapy , Simvastatin/adverse effects , Tendon Injuries/chemically induced , Tendons/drug effects , Animals , Atorvastatin/therapeutic use , Collagen Type I/metabolism , Enzyme Precursors/metabolism , Gelatinases/metabolism , Glycosaminoglycans/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hydroxyproline/metabolism , Male , Rats , Rats, Wistar , Simvastatin/therapeutic use
16.
Braz J Med Biol Res ; 50(1): e5511, 2017 Jan 09.
Article in English | MEDLINE | ID: mdl-28076450

ABSTRACT

Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days), sub-acute (7 days) and chronic (28 days) phases of myocardial infarction (MI) in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV) and heart rate variability (HRV). Pulsatile blood pressure (BP) recordings (30 min) were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old) with MI (coronary ligature) or sham operation (SO). Data are reported as means±SE. The high frequency (HF) component (n.u.) of HRV was significantly lower in MI-1- (P<0.01) and MI-3-day rats (P<0.05) than in their time-control groups (SO-1=68±4 vs MI-1=35.3±4.3; SO-3=71±5.8 vs MI-3=45.2±3.8), without differences thereafter (SO-7=69.2±4.8 vs MI-7=56±5.8; SO-28=73±4 vs MI-28=66±6.6). A sharp reduction (P<0.05) of BPV (mmHg2) was observed in the first week after MI (SO-1=8.55±0.80; SO-3=9.11±1.08; SO-7=7.92±1.10 vs MI-1=5.63±0.73; MI-3=5.93±0.30; MI-7=5.30±0.25). Normal BPV, however, was observed 4 weeks after MI (SO-28=8.60±0.66 vs MI-28=8.43±0.56 mmHg2; P>0.05). This reduction was mainly due to attenuation of the low frequency (LF) band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%). The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance.


Subject(s)
Autonomic Nervous System/physiopathology , Blood Pressure/physiology , Heart Rate/physiology , Myocardial Infarction/physiopathology , Acute Disease , Animals , Baroreflex/physiology , Blood Pressure Determination , Chronic Disease , Disease Models, Animal , Male , Rats , Rats, Wistar
17.
Environ Toxicol Pharmacol ; 48: 286-293, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27866098

ABSTRACT

The present study evaluates the superoxide dismutase (SOD) and catalase (CAT) activities in a wild strain of Drosophila melanogaster and the genotoxic potential induced by Cas II-gly (a new antineoplastic drug) using the somatic mutation and recombination test. Larvae 48h old were treated with Cas II-gly in a range of 0-1.5mM and aliquot were taken every 24h to have individuals treated for 24, 48, 72h and adulthood as well. A dose-dependent toxicity and a significant increase in SOD and CAT activities were found after a 24 and 48h treatment with 0.5-1.5mM concentrations. The comparison of the effect in enzymes with mutation indicated a positive correlation with increased genetic damage, after 24 and 48h of exposure for all concentrations tested. The addition of the genetic damage induced in each exposure time showed a significant effect, but only the small single spots had a concentration-related increase.


Subject(s)
Antineoplastic Agents/toxicity , Chelating Agents/toxicity , Copper/metabolism , Mutagens/toxicity , Organometallic Compounds/toxicity , Oxidative Stress/drug effects , Animals , Catalase/metabolism , Dose-Response Relationship, Drug , Drosophila melanogaster/drug effects , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Female , Lethal Dose 50 , Lipid Peroxidation/drug effects , Lipid Peroxidation/genetics , Male , Oxidative Stress/genetics , Recombination, Genetic/drug effects , Superoxide Dismutase/metabolism , Wings, Animal/drug effects
18.
J Dairy Sci ; 99(3): 1999-2004, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26723131

ABSTRACT

In this study we investigate the potential of enlarging the reference population for genomic prediction in dairy cattle by routinely genotyping a random sample of the first-crop daughters of every AI bull in the breeding program. We analyzed small nuclear pedigrees, each consisting of a genotyped selection candidate and 3 generations of genotyped male ancestors. Genotypes were taken from the genomic routine evaluation of Fleckvieh cattle in Germany and Austria. The phenotypic information of a daughter of any one male in each of these pedigrees was either considered to be part of the daughter yield deviation of the corresponding sire, or was assumed to be an individually observed genotyped daughter of this sire. Daughter genotypes in this case were simulated from phased haplotypes of their sires and random maternal gametes drawn from a haplotype library. We measured the gain from genotyping daughters as the increase in model-based theoretical reliability of the genomic prediction for a putative selection candidate. We expressed the improvements as a marginal increase, corresponding to an increase in reliability at a reliability baseline level of zero, to simplify comparisons. Results were encouraging with 2 to 40% of marginal reliability increase for selection candidates depending on the assumed heritability of the trait and the number of daughters modeled to be genotyped in the design.


Subject(s)
Cattle/genetics , Genotype , Selection, Genetic , Animals , Austria , Breeding , Female , Genome , Genomics/methods , Germany , Haplotypes , Male , Pedigree , Phenotype , Reproducibility of Results
19.
Braz J Med Biol Res ; 48(8): 728-35, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26132095

ABSTRACT

High salt intake is related to an increase in blood pressure and development of hypertension. However, currently, there are no national representative data in Brazil using the gold standard method of 24-h urine collection to measure sodium consumption. This study aimed to determine salt intake based on 24-h urine collection in a sample of 272 adults of both genders and to correlate it with blood pressure levels. We used a rigorous protocol to assure an empty bladder prior to initiating urine collection. We excluded subjects with a urine volume <500 mL, collection period outside of an interval of 23-25 h, and subjects with creatinine excretion that was not within the range of 14.4-33.6 mg/kg (men) and 10.8-25.2 mg/kg (women). The mean salt intake was 10.4±4.1 g/day (d), and 94% of the participants (98% of men and 90% of women) ingested more than the recommended level of 5 g/d. We found a positive association between salt and body mass index (BMI) categories, as well as with salt and blood pressure, independent of age and BMI. The difference in systolic blood pressure reached 13 mmHg between subjects consuming less than 6 g/d of salt and those ingesting more than 18 g/d. Subjects with hypertension had a higher estimated salt intake than normotensive subjects (11.4±5.0 vs 9.8±3.6 g/d, P<0.01), regardless of whether they were under treatment. Our data indicate the need for interventions to reduce sodium intake, as well the need for ongoing, appropriate monitoring of salt consumption in the general population.


Subject(s)
Blood Pressure/physiology , Sodium Chloride, Dietary/administration & dosage , Sodium/urine , Adult , Blood Pressure/drug effects , Brazil , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Time Factors , Urban Population , Urine Specimen Collection/methods
20.
J Dairy Sci ; 98(6): 4131-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25841966

ABSTRACT

The objective of this study was to investigate in detail the biasing effects of imputation errors on genomic predictions. Direct genomic values (DGV) of 3,494 Brown Swiss selection candidates for 37 production and conformation traits were predicted using either their observed 50K genotypes or their 50K genotypes imputed from a mimicked 6K chip. Changes in DGV caused by imputation errors were shown to be systematic. The DGV of top animals were, on average, underestimated and that of bottom animals were, on average, overestimated when imputed genotypes were used instead of observed genotypes. This pattern might be explained by the fact that imputation algorithms will usually suggest the most frequent haplotype from the sample whenever a haplotype cannot be determined unambiguously. That was empirically shown to cause an advantage for the bottom animals and a disadvantage for the top animals.


Subject(s)
Breeding , Cattle/genetics , Genome , Genomics/methods , Algorithms , Animals , Austria , Germany , Haplotypes , Models, Genetic , Oligonucleotide Array Sequence Analysis/veterinary
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