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1.
SAR QSAR Environ Res ; 32(2): 151-174, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33525942

RESUMO

One step towards reduced animal testing is the use of in silico screening methods to predict toxicity of chemicals, which requires high-quality data to develop models that are reliable and clearly interpretable. We compiled a large data set of fish early life stage no observed effect concentration endpoints (FELS NOEC) based on published data sources and internal studies, containing data for 338 molecules. Furthermore, we developed a new quantitative structure-activity-activity relationship (QSAAR) model to inform estimation of this endpoint using a combination of dimensionality reduction, regularization, and domain knowledge. In particular, we made use of a sparse partial least squares algorithm (sPLS) to select relevant variables from a huge number of molecular descriptors ranging from topological to quantum chemical properties. The final QSAAR model is of low complexity, consisting of 2 latent variables based on 8 molecular descriptors and experimental Daphnia magna acute data (EC50, 48 h). We provide a mechanistic interpretation of each model parameter. The model performs well, with a coefficient of determination r 2 of 0.723 on the training set (cross-validated q 2 = 0.686) and comparable predictivity on a test data set of chemically related molecules with experimental Daphnia magna data (r 2 test = 0.687, RMSE = 0.793 log units).


Assuntos
Daphnia/efeitos dos fármacos , Peixes/metabolismo , Larva/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Testes de Toxicidade/veterinária , Animais , Análise dos Mínimos Quadrados , Modelos Biológicos , Testes de Toxicidade/instrumentação
2.
Arq. bras. med. vet. zootec. (Online) ; 71(5): 1582-1590, set.-out. 2019. tab, ilus
Artigo em Português | LILACS, VETINDEX | ID: biblio-1038681

RESUMO

Hemigrammus caudovittatus e Danio rerio foram expostos aos hipoglicemiantes orais (HOs) cloridrato de metformina a 40µg/L e 120µg/L e glibenclamida a 0,13µg/L e 0,39µg/L durante 100 dias. Foram avaliados os efeitos tóxicos dos fármacos em relação ao peso, ao comportamento animal, à glicemia e à mortalidade. H. caudovittatus expostos à menor concentração dos fármacos apresentaram aumento significativo (P<0,05) no evento Respiração Aérea. Ainda, foi observado aumento no comportamento Descansar quando os animais foram expostos à glibenclamida a 0,39µg/L. Em D. rerio expostos ao cloridrato de metformina a 120µg/L, foi observado aumento (P<0,05) no comportamento Descansar. A glibenclamida provocou redução (P<0,05) na glicemia de H. caudovittatus. Ambos os fármacos causaram efeito letal na espécie D. rerio, contudo a glibenclamida foi mais tóxica, causando 100% de mortalidade em 30 dias de exposição. Os animais que vieram a óbito apresentaram congestão nos arcos branquiais e hemorragia. Os HOs foram desenvolvidos para apresentarem efeitos fisiológicos em mamíferos, entretanto efeitos tóxicos foram encontrados nas duas espécies de peixe estudadas. Isso levanta a preocupação sobre possíveis efeitos tóxicos de HOs e sobre quais métodos serão utilizados para a sua degradação no ambiente aquático.(AU)


Hemigrammus caudovittatus and Danio rerio were exposed to oral hypoglycemic drugs (HOs) metformin hydrochloride at 40µg/L and 120µg/L and to glibenclamide at 0.13µg/L and 0.39µg/L during 100 days. Toxic effects of the drugs were evaluated based on weight, animal behavior, blood glucose and mortality. H. caudovittatus exposed to lowest concentration of the drugs showed significant increase (P< 0.05) in the Air breathing event. Furthermore, increase in Rest event was observed when animals were exposed to glibenclamide at 0.39µg/L. An increase (P< 0.05) in the frequency of Rest behavior in the D. rerio exposed to metformin hydrochloride at 120µg/L was observed. Glibenclamide caused decrease (P< 0.05) in the blood glucose of H. caudovittatus. Both drugs caused lethal effect against D. rerio. Nevertheless, glibenclamide was more toxic causing 100% of mortality after 30 days of exposure. The animals that died showed congestion on the branchial arches and hemorrhage. The HOs were developed to have physiological effects in mammals. However, toxic effects were found in both species of fish studied. This raises concerns about possible toxic effects of HOs and what methods will be used for their degradation in the aquatic environment.(AU)


Assuntos
Animais , Peixe-Zebra , Glibureto/toxicidade , Testes de Toxicidade/veterinária , Resíduos Químicos , Characidae , Hipoglicemiantes/toxicidade , Metformina/toxicidade , Modelos Animais
3.
Artigo em Inglês | MEDLINE | ID: mdl-31547363

RESUMO

The proliferation of cellular antennas and other radiofrequency radiation (RFR) generating devices of the last decades has led to more and more concerns about the potential health effects from RFR exposure. Since the 2011 classification as a possible carcinogen by the International Agency for Research on Cancer (IARC), more experimental studies have been published that support a causal association between RFR exposure and health hazards. As regard cancer risk, two long-term experimental studies have been recently published by the US National Toxicology Program (NTP) and the Italian Ramazzini Institute (RI). Despite important experimental differences, both studies found statistically significant increases in the development of the same type of very rare glial malignant tumors. In addition to carcinogenicity, reproductive organs might be particularly exposed, as well as sensitive to RFR. In this work, we reviewed the currently available evidence from in vivo studies on carcinogenicity and reproductive toxicity studies in order to summarize the contribution of experimental research to the prevention of the adverse effects of RFR on human health.


Assuntos
Exposição à Radiação/efeitos adversos , Ondas de Rádio/efeitos adversos , Reprodução/efeitos da radiação , Animais , Testes de Carcinogenicidade/estatística & dados numéricos , Testes de Carcinogenicidade/veterinária , Humanos , Testes de Toxicidade/estatística & dados numéricos , Testes de Toxicidade/veterinária
4.
J Vet Med Sci ; 81(8): 1129-1132, 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31270308

RESUMO

Veterinary vaccines are subjected to a safety testing using laboratory animals via intraperitoneal injection per batch. From April 2010 to March 2011, 7 guinea pigs in 4 batch tests exhibited unrecoverable weight loss and/or were found dead. Six guinea pigs had developed intussusception, whereas another one had developed an intestinal obstruction consequent to adhesion. A histopathology revealed that these lesions were associated with inflammatory foci. Other animals than the 7 guinea pig also developed similar inflammatory foci but did not develop bowel disorders. In the retesting of these batches, animals did not exhibited clinical signs, though inflammatory foci were detected. The clinical signs, detected in the primary test, might be due to bowel disorders secondary to an inflammatory response, rather than toxicity.


Assuntos
Doenças Inflamatórias Intestinais/veterinária , Testes de Toxicidade/veterinária , Vacinas/efeitos adversos , Animais , Cobaias , Doenças Inflamatórias Intestinais/etiologia , Injeções Intraperitoneais , Vacinas/administração & dosagem
5.
J Vet Sci ; 20(2): e14, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30944536

RESUMO

With the increased use of cell therapy in the veterinary sector, there is a growing demand for the development of cell-based medicinal products and the determination of their safety. Currently, the Korean Animal and Plant Quarantine Agency has established a guideline for evaluating the safety of cell-based medicinal products for animal use. The guideline includes items related to definition, classification, management, manufacturing procedure and quality control (standard and test method), stability testing, toxicity testing, pharmacological testing, and performance of clinical trials. In addition, testing protocols related to safety assessment of animal cell-based products such as chromosome karyotyping, tumorigenicity testing, confirmatory testing of biodistribution and kinetics, and target animal safety testing are described in detail. Moreover, because cell-based medicinal products are novel therapies, deviations from traditional designs may be justified in order to obtain relevant safety information on the treatment. Additionally, this guideline can be amended on the basis of new scientific findings.


Assuntos
Produtos Biológicos/normas , Testes de Toxicidade/veterinária , Animais , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Ensaios Clínicos Veterinários como Assunto , Testes de Toxicidade/métodos , Testes de Toxicidade/normas
6.
Toxicol Pathol ; 45(8): 1055-1066, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29233079

RESUMO

To test the diagnostic approach described in part 1 of this article, 2 exercises were completed by pathologists from multiple companies/agencies. Pathologist's examination of whole slide image (WSI) heart sections from rats using personal diagnostic approaches (exercise #1) corroborated conclusions from study #1. Using the diagnostic approach described in part 1, these pathologists examined the same WSI heart sections (exercise #2) to determine whether that approach increased consistency of diagnosis of rodent progressive cardiomyopathy (PCM) lesions. In exercise #2, there was improved consistency of categorization of small borderline morphologies and mild lesions, but a decrement in consistency of categorizing minimal lesions. Exercises 1 and 2 suggest the described diagnostic approach is representative of that in use by the majority of toxicologic pathologists across companies/agencies and that application by all may improve diagnostic consistency of PCM/like lesions. Additionally, a criterion of approximately 5% heart section involvement is suggested for separating mild from moderate or greater severity. While evidence is not absolute, until further investigation shows otherwise, microscopic changes resembling PCM, but located in the epicardial and subepicardial region of the right ventricle, may be considered as part of the spectrum of PCM.


Assuntos
Cardiomiopatias/patologia , Diagnóstico por Imagem/métodos , Ventrículos do Coração/patologia , Ratos Sprague-Dawley , Doenças dos Roedores/patologia , Testes de Toxicidade/métodos , Animais , Cardiomiopatias/veterinária , Cardiotoxicidade/patologia , Cardiotoxicidade/veterinária , Simulação por Computador , Diagnóstico por Imagem/normas , Diagnóstico por Imagem/veterinária , Progressão da Doença , Masculino , Testes de Toxicidade/veterinária
7.
Toxicol Pathol ; 45(8): 1043-1054, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29173114

RESUMO

Spontaneous rodent progressive cardiomyopathy (PCM) in the Sprague Dawley rat may confound identification and/or interpretation of potential test article (TA)-related cardiotoxicity. Pathologists apply diagnostic term(s) and thresholds for diagnosing and assigning severity grades for PCM and/or PCM-like (PCM/like) lesions consistently within a study, which is necessary to identify and interpret TA-related findings. Due to differences in training and/or experiences, diagnostic terms and thresholds may vary between pathologists. Harmonized terminology and thresholds across studies will generate better historical control data, will likely enhance interpretation of study data, and may further enhance our understanding of the spontaneous change. An assessment of the diagnostic approaches of a group of 37 pathologists identified an approach that is relatively easily applied; and if adopted, it could enhance diagnostic consistency across studies. This approach uses the single "slash" term "necrosis/inflammatory cell infiltrate (NICI)" as the diagnosis for the spectrum of lesions seen in younger rats, uses no threshold for diagnosis (e.g., diagnose all lesions clearly identifiable as PCM/like), and uses aggregate lesion size of approximately ≥45% of the field of view (FOV) using a 10×/22 eyepiece and the 40× objective or approximately ≥100% of the FOV using the 60× objective as the criterion separating minimal from mild severities.


Assuntos
Cardiomiopatias/patologia , Diagnóstico por Imagem/métodos , Ratos Sprague-Dawley , Doenças dos Roedores/patologia , Testes de Toxicidade/veterinária , Animais , Cardiomiopatias/veterinária , Cardiotoxicidade/patologia , Cardiotoxicidade/veterinária , Simulação por Computador , Diagnóstico por Imagem/normas , Diagnóstico por Imagem/veterinária , Progressão da Doença , Masculino , Necrose , Índice de Gravidade de Doença
8.
Toxicol Pathol ; 45(2): 275-280, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28178898

RESUMO

Preanalytical variables can have significant impacts on clinical pathology parameters evaluated during the conduct of a nonclinical safety or toxicity study. These preanalytical variables can be controlled by careful attention to factors such as animal dietary status (diet composition, fasted, and fed state), restraint and anesthesia, intercurrent procedures, timing of clinical pathology collections, and proficiency of animal technicians. The impact of preanalytical variables on test results can be significant enough to result in difficult interpretations and/or regulatory questions or can obfuscate the effects of a test article. Control of preanalytical variables starts with knowledge of what processes and procedures impact test results. Minimizing these effects improves the quality of results and maximizes the value of the study.


Assuntos
Coleta de Amostras Sanguíneas/normas , Técnicas de Laboratório Clínico/normas , Guias como Assunto , Patologia Clínica/normas , Testes de Toxicidade/normas , Animais , Coleta de Amostras Sanguíneas/veterinária , Técnicas de Laboratório Clínico/veterinária , Dieta , Jejum , Controle de Qualidade , Restrição Física , Testes de Toxicidade/veterinária
9.
Toxicol Pathol ; 45(2): 260-266, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28056663

RESUMO

There is limited direction in the literature or regulatory guidance on determination of adversity for clinical pathology (CP) biomarkers in preclinical safety studies. Toxicologic clinical pathologists representing the American Society for Veterinary Clinical Pathology-Regulatory Affairs Committee and Society of Toxicologic Pathology-Clinical Pathology Interest Group identified principles, overall approach, and unique considerations for assessing adversity in CP data interpretation to provide a consensus opinion. Emphasized is the need for pathophysiologic context and a weight-of-evidence approach. Most CP biomarkers do not have the potential to be adverse in isolation, regardless of magnitude of change. Rather, they quantify or describe the impact of effects, provide adjunct or supportive information regarding a process or pathogenesis, and provide translational biomarkers of effect. Most often, CP changes are part of a constellation of findings that collectively are adverse. Thus, most CP changes must be interpreted in conjunction with other study findings and require contextual and integrative interpretation. Exceptions include critical CP changes without correlates that indicate a health risk in the tested species. Overall, CP changes should not be interpreted in isolation and their adversity is best addressed with an integrated approach.


Assuntos
Biomarcadores/análise , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Guias como Assunto , Patologia Clínica/normas , Patologia Veterinária/normas , Testes de Toxicidade/normas , Animais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/veterinária , Humanos , Nível de Efeito Adverso não Observado , Controle de Qualidade , Medição de Risco , Testes de Toxicidade/veterinária
10.
Toxicol Pathol ; 45(2): 267-274, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27879436

RESUMO

Cytological bone marrow evaluation is utilized in nonclinical toxicology studies to characterize hematopoietic effects when the combined interpretation of histologic and complete blood count data does not yield sufficient information. Results from cytological bone marrow examination should be interpreted in the context of variability observed in concurrent control animals with consideration of cytologist experience and historical/published data. Cytological bone marrow differential counts and cellular morphologic findings from 130 (66 male, 64 female) healthy control cynomolgus monkeys from nonclinical toxicology studies were retrospectively analyzed. Myeloid to erythroid (M:E) ratios and the percentage of total cells for each cell type were determined from differential cell count data. M:E ratios ranged from 0.6:1 to 2.3:1. Percentages of total granulocytic cells, total erythroid cells, and lymphocytes ranged from 26.6% to 60.6%, 25.7% to 52.2%, and 5.5% to 40.4%, respectively. Monocytes, plasma cells, mast cells, and mitotic figures were typically <1% of total cells. Notable morphologic findings included occasional giant neutrophilic metamyelocytes and band neutrophils, ring-shaped band neutrophil nuclei, metarubricyte nuclear blebbing and binucleation, multiple or nonfused megakaryocyte nuclei, and emperipolesis. These results represent cytological bone marrow findings from healthy control cynomolgus monkeys utilized in nonclinical toxicology studies and provide insight into expected background variability.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Exame de Medula Óssea , Guias como Assunto , Macaca fascicularis , Testes de Toxicidade/métodos , Animais , Contagem de Células Sanguíneas , Exame de Medula Óssea/veterinária , Feminino , Masculino , Caracteres Sexuais , Manejo de Espécimes/veterinária , Testes de Toxicidade/veterinária
11.
Toxicol Pathol ; 45(2): 296-301, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28007014

RESUMO

Gastric mucosal injury is frequently observed in nonclinical studies of nonhuman primates. Because microscopic evaluation of stomach is generally a terminal procedure, our objective was to determine whether serum pepsinogen I (PG I) could serve as a noninvasive biomarker for detection of gastric mucosal injury in monkey. Serum PG I was measured using a commercial human immunoassay in cynomolgus monkeys ( n = 166) prior to dosing and/or terminally in 11 studies of up to 1 month duration. Mean ( SD) PG I values (ug/L) for monkeys with ( n = 59) and without ( n = 100) gastric mucosal degeneration were 101 (215) and 28 (12.6), respectively. For monkeys with baseline and terminal PG I data, mean ( SD) fold change (ratio of terminal to baseline PG I) for monkeys with ( n = 57) and without ( n = 76) glandular degeneration were 4.1 (11.3) and 1 (0.28). Receiver operating characteristic area under the curve (AUC) data demonstrated moderate diagnostic accuracy for serum PG I for glandular degeneration, AUC ( SE) 0.789 (0.04), with improved diagnostic accuracy as a fold change of baseline, AUC ( SE) 0.816 (0.04), consistent with the large interindividual but low intraindividual variability of serum PG I values in control monkeys. These data demonstrate that serum PG I is a useful biomarker of drug-induced gastric mucosal injury in the cynomolgus monkey.


Assuntos
Avaliação Pré-Clínica de Medicamentos/normas , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Pepsinogênio A/sangue , Testes de Toxicidade/normas , Animais , Biomarcadores/sangue , Avaliação Pré-Clínica de Medicamentos/veterinária , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Feminino , Macaca fascicularis , Masculino , Estudos Retrospectivos , Testes de Toxicidade/veterinária
12.
Arch Environ Contam Toxicol ; 72(2): 269-280, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27990605

RESUMO

The simultaneous profiling of 43 functional metabolites in the brain of the small model vertebrate organism, marine medaka (Oryzais melastigma), has been accomplished via dansyl chloride derivatization and LC-MS/MS quantification. This technique was applied to examine effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), one of the most abundant polybrominated diphenyl ether flame retardants in the natural environment, on the central nervous system (CNS) of vertebrates. The model teleosts were fed with bioencapsulated Artemia nauplii for up to 21 days. Multivariate statistical analysis has demonstrated that levels of numerous classical neurotransmitters and their metabolites in the CNS of the fish were perturbed even at the early phase of dietary exposure. Subsequent metabolic pathway analysis further implied potential impairment of the arginine and proline metabolism; glycine, serine and threonine metabolism; D-glutamine and D-glutamate metabolism; alanine, aspartate, and glutamate metabolism; valine, leucine, and isoleucine biosynthesis, and the cysteine and methionine metabolism in the brain of the test organism. Our results demonstrate that targeted profiling of functional metabolites in the CNS may shed light on how the various neurological pathways of vertebrates, including humans, are affected by toxicant/stress exposure.


Assuntos
Éteres Difenil Halogenados/toxicidade , Neurotransmissores/metabolismo , Oryzias/metabolismo , Testes de Toxicidade/veterinária , Poluentes Químicos da Água/toxicidade , Animais , Sistema Nervoso Central/efeitos dos fármacos , Cromatografia Líquida/veterinária , Compostos de Dansil/química , Retardadores de Chama/toxicidade , Espectrometria de Massas em Tandem/veterinária , Testes de Toxicidade/métodos
13.
J Fish Dis ; 39(10): 1201-12, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27038351

RESUMO

Egg strings and nauplii of the salmon louse Lepeophtheirus salmonis were exposed to a variety of medicinal compounds at 50 mg L(-1) for 30 min in two experiment series. This medicine concentration was selected as a starting point for a screening series. Hatching of egg strings and development to copepodid larvae were monitored in one experiment, and the survival and development of nauplii were monitored in the other. Two compounds, emamectin benzoate and cypermethrin, inhibited hatching effectively. Several compounds affected nauplii, either directly or through inhibiting development to the infective stage. A total of 50 mg L(-1) of azamethiphos, cypermethrin, emamectin benzoate and propoxur was lethal to >70% of the larvae. Diflubenzuron, fenoxycarb, pymetrozine, pyriprole and tebufenozide diminished the ability of nauplii developing to copepodids.


Assuntos
Copépodes/efeitos dos fármacos , Ectoparasitoses/veterinária , Doenças dos Peixes/prevenção & controle , Praguicidas/farmacologia , Testes de Toxicidade/veterinária , Animais , Ectoparasitoses/parasitologia , Ectoparasitoses/prevenção & controle , Feminino , Doenças dos Peixes/parasitologia , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Masculino , Óvulo/efeitos dos fármacos
14.
Theriogenology ; 82(3): 387-95, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24877724

RESUMO

The development and optimization of preantral follicle culture methods are crucial in fertility preservation strategies. As preantral follicle dynamics are usually assessed by various invasive techniques, the need for alternative noninvasive evaluation tools exists. Recently, neutral red (NR) was put forward to visualize preantral follicles in situ within ovarian cortical fragments. However, intense light exposure of NR-stained tissues can lead to cell death because of increased reactive oxygen species production, which is also associated with elevated oxygen tension. Therefore, we hypothesize that after repeated NR staining, follicle viability and dynamics can be altered by changes in oxygen tension. In the present study, we aim (1) to determine whether NR can be used to repeatedly assess follicular growth, activation, and viability and (2) to assess the effect of a low (5% O2) or high (20% O2) oxygen tension on the viability, growth, and stage transition of preantral follicles cultured in vitro by means of repeated NR staining. Cortical slices (n = 132; six replicates) from bovine ovaries were incubated for 3 hours at 37 °C in a Leibovitz medium with 50 µg/mL NR. NR-stained follicles were evaluated in situ for follicle diameter and morphology. Next, cortical fragments were individually cultured in McCoy's 5A medium for 6 days at 37 °C, 5% CO2, and 5% or 20% O2. On Days 4 and 6, the fragments were restained by adding NR to the McCoy's medium and follicles were reassessed. In both low and high oxygen tension treatment groups, approximately 70% of the initial follicles survived a 6-day in vitro culture, but no significant difference in follicle survival on Day 4 or 6 could be observed compared with Day 0 (P > 0.05). A significant decrease in the number of primordial and increase in primary and secondary follicles was observed within 4 days of culture (P < 0.001). In addition, a significant increase of the mean follicle diameter in NR-stained follicles was observed (P < 0.001), resulting in an average growth of 11.82 ± 0.81 µm (5% O2) and 11.78 ± 1.06 µm (20% O2) on Day 4 and 20.94 ± 1.24 µm (5% O2) and 19.12 ± 1.36 µm (20% O2) on Day 6 compared with Day 0. No significant differences in follicle growth rate or stage transition could be observed between 5% and 20% O2 (P > 0.05). In conclusion, after repeated NR staining, we could not find a difference between low and high oxygen tension in terms of follicle viability, stage transition, or growth. Therefore, under our culture conditions follicle dynamics are not determined by the oxygen tension in combination with quality assessment protocols using repeated NR staining.


Assuntos
Técnicas de Cultura de Células/veterinária , Vermelho Neutro/toxicidade , Folículo Ovariano/fisiologia , Animais , Bovinos , Feminino , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade/veterinária
15.
Exp Toxicol Pathol ; 66(5-6): 263-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24795276

RESUMO

An incidental, asymptomatic, focal inflammatory lesion was detected in brain cerebrum of an approximately 6-year-old, female cynomolgus macaque from a chronic toxicology study. No gross lesions were noted at necropsy. Microscopically, the lesion contained a cross-section of larvae approximately 70-80 µm in diameter, a centrally located intestine flanked on either side by large triangular excretory columns, and prominent single lateral cuticular alae. Mixed inflammatory cells of eosinophils, macrophages, and lymphocytes admixed with abundant connective tissue stroma and necrosis surrounded the larvae. Histochemical stains for trichrome revealed significant amount of fibrous connective tissue. The morphology of the larvae was compatible with Baylisascaris spp. Based on the microscopic and histochemical examination, a diagnosis of neural Baylisascaris spp. larva migrans was made.


Assuntos
Infecções por Ascaridida/veterinária , Ascaridoidea/isolamento & purificação , Encéfalo/parasitologia , Helmintíase Animal/parasitologia , Larva Migrans/veterinária , Doenças dos Macacos/parasitologia , Animais , Infecções por Ascaridida/parasitologia , Infecções por Ascaridida/patologia , Encéfalo/patologia , Feminino , Helmintíase Animal/patologia , Larva Migrans/parasitologia , Larva Migrans/patologia , Macaca fascicularis , Doenças dos Macacos/patologia , Testes de Toxicidade/veterinária
16.
Sci Total Environ ; 468-469: 630-41, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24061054

RESUMO

Aquaculture production constitutes one of the main sources of pollution with veterinary medicines into the environment. About 90% of the global aquaculture production is produced in Asia and the potential environmental risks associated with the use of veterinary medicines in Asian aquaculture have not yet been properly evaluated. In this study we performed a probabilistic risk assessment for eight different aquaculture production scenarios in Asia by combining up-to-date information on the use of veterinary medicines and aquaculture production characteristics. The ERA-AQUA model was used to perform mass balances of veterinary medicinal treatments applied to aquaculture ponds and to characterize risks for primary producers, invertebrates, and fish potentially exposed to chemical residues through aquaculture effluents. The mass balance calculations showed that, on average, about 25% of the applied drug mass to aquaculture ponds is released into the environment, although this percentage varies with the chemical's properties, the mode of application, the cultured species density, and the water exchange rates in the aquaculture pond scenario. In general, the highest potential environmental risks were calculated for parasitic treatments, followed by disinfection and antibiotic treatments. Pangasius catfish production in Vietnam, followed by shrimp production in China, constitute possible hot-spots for environmental pollution due to the intensity of the aquaculture production and considerable discharge of toxic chemical residues into surrounding aquatic ecosystems. A risk-based ranking of compounds is provided for each of the evaluated scenarios, which offers crucial information for conducting further chemical and biological field and laboratory monitoring research. In addition, we discuss general knowledge gaps and research priorities for performing refined risk assessments of aquaculture medicines in the near future.


Assuntos
Aquicultura/métodos , Peixes-Gato/metabolismo , Exposição Ambiental , Penaeidae/metabolismo , Medição de Risco/métodos , Drogas Veterinárias/farmacocinética , Poluentes Químicos da Água/farmacocinética , Animais , Aquicultura/estatística & dados numéricos , Ásia , Modelos Biológicos , Testes de Toxicidade/veterinária , Drogas Veterinárias/metabolismo , Poluentes Químicos da Água/metabolismo
17.
J Med Entomol ; 50(3): 668-73, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23802465

RESUMO

The Asian tiger mosquito Aedes albopictus (Skuse, 1894) is a globally invasive prominent vector of viral and parasitic pathogens. To soundly guide insecticide use in control programs it is crucial to use standardized test systems under rigorously controlled environmental conditions that allow for comparisons across laboratories. An acute standard test procedure (24 h) for insecticide resistance monitoring of mosquitoes has been published by the World Health Organization in 1998, but a standardized chronic test to monitor sublethal insecticide effects on the life cycle of mosquitoes does not yet exist. As a first step toward a standardized chronic bioassay (half-life-cycle-test), the exclusion of qualitative and quantitative food effects by means of standardized, optimal larval feeding would greatly facilitate inter-laboratory comparisons. Against this background we evaluated food qualities and quantities for the aquatic part of the A. albopictus life cycle under different thermal conditions. Five mg TetraMin (Tetra, Melle, Germany) larva(-1) at 25 degrees C rendered the lowest mortality and large pupae. Our fundamental data on A. albopictus feeding provide an opportunity to standardize experiments and thus support interlaboratory comparisons of studies on the ecotoxicology of this dangerous vector mosquito.


Assuntos
Aedes/fisiologia , Ração Animal/análise , Testes de Toxicidade/métodos , Aedes/crescimento & desenvolvimento , Animais , Dieta/veterinária , Feminino , Qualidade dos Alimentos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Masculino , Pupa/crescimento & desenvolvimento , Pupa/fisiologia , Temperatura , Testes de Toxicidade/veterinária
18.
N Biotechnol ; 30(4): 349-54, 2013 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-23253614

RESUMO

Despite the fact that a thorough, lengthy and costly evaluation of genetically engineered (GE) crop plants (including compositional analysis and toxicological tests) is imposed before marketing some European citizens remain sceptical of the safety of GE food and feed. In this context, are additional tests necessary? If so, what can we learn from them? To address these questions, we examined data from 60 recent high-throughput '-omics' comparisons between GE and non-GE crop lines and 17 recent long-term animal feeding studies (longer than the classical 90-day subchronic toxicological tests), as well as 16 multigenerational studies on animals. The '-omics' comparisons revealed that the genetic modification has less impact on plant gene expression and composition than that of conventional plant breeding. Moreover, environmental factors (such as field location, sampling time, or agricultural practices) have a greater impact than transgenesis. None of these '-omics' profiling studies has raised new safety concerns about GE varieties; neither did the long-term and multigenerational studies on animals. Therefore, there is no need to perform such long-term studies in a case-by-case approach, unless reasonable doubt still exists after conducting a 90-day feeding test. In addition, plant compositional analysis and '-omics' profiling do not indicate that toxicological tests should be mandatory. We discuss what complementary fundamental studies should be performed and how to choose the most efficient experimental design to assess risks associated with new GE traits. The possible need to update the current regulatory framework is discussed.


Assuntos
Inocuidade dos Alimentos/métodos , Alimentos Geneticamente Modificados/efeitos adversos , Alimentos Geneticamente Modificados/normas , Plantas Geneticamente Modificadas/genética , Medição de Risco/métodos , Ração Animal/efeitos adversos , Animais , Perfilação da Expressão Gênica , Humanos , Testes de Toxicidade/veterinária
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