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1.
Reprod Toxicol ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278556

RESUMO

25 years after the first Berlin Workshop on Developmental Toxicity this 10th Berlin Workshop aimed to bring together international experts from authorities, academia and industry to consider scientific, methodologic and regulatory aspects in risk assessment of developmental toxicity and to debate alternative strategies in testing developmental effects in the future. Proposals for improvement of the categorization of developmental effects were discussed as well as the update of the DevTox database as valuable tool for harmonization. The development of adverse outcome pathways relevant to developmental neurotoxicity (DNT) was debated as a fundamental improvement to guide the screening and testing for DNT using alternatives to animal methods. A further focus was the implementation of an in vitro mechanism-based battery, which can support various regulatory applications associated with the assessment of chemicals and mixtures. More interdisciplinary and translation research should be initiated to accelerate the development of new technologies to test developmental toxicity. Technologies in the pipeline are (i) high throughput imaging techniques, (ii) models for DNT screening tests, (iii) use of computer tomography for assessment of thoracolumbar supernumerary ribs in animal models, and (iv) 3D biofabrication of bone development and regeneration tissue models. In addition, increased collaboration with the medical community was suggested to improve the relevance of test results to humans and identify more clinically relevant endpoints. Finally, the participants agreed that this conference facilitated better understanding innovative approaches that can be useful for the identification of developmental health risks due to exposure to chemical substances.

2.
Reprod Toxicol ; 89: 124-129, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31288076

RESUMO

Representatives of applied science (e.g. governmental organizations, academia, and industry) met to discuss the progress towards a harmonized human health risk assessment in developmental toxicology of plant protection products, biocidal products, and other environmental chemicals at the 9th Berlin Workshop on Developmental Toxicity held in September 2018. Within the focus of the scientific discussion were the future of in-vitro methods for developmental and reproductive toxicology, the potential relevance of alternative species in testing of developmental effects, and risk and hazard assessment of developmental and endocrine effects. Furthermore, the need for a harmonized terminology for classification of anomalies in laboratory animals in developmental toxicity studies aiming for human health risk assessment was determined. Here, the DevTox database was identified as an extremely valuable tool. Overall, the participants agreed that still one of the biggest challenges for testing developmental toxicity in the 21st century is the development of animal-free test strategies and alternatives to animal testing that could provide human-relevant information in a rapid, efficient, and mechanistically informative manner.


Assuntos
Alternativas ao Uso de Animais/métodos , Bases de Dados Factuais/tendências , Reprodução/efeitos dos fármacos , Toxicologia/métodos , Alternativas ao Uso de Animais/tendências , Animais , Berlim , Medição de Risco , Especificidade da Espécie , Terminologia como Assunto , Toxicologia/tendências
3.
Genes (Basel) ; 9(5)2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29748516

RESUMO

Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells and an extracellular matrix that is mechanically stable, yet flexible at the same time. Unlike most tissues, bone is under constant renewal facilitated by a coordinated interaction of bone-forming and bone-resorbing cells. It is thus challenging to recreate bone in its complexity in vitro and most current models rather focus on certain aspects of bone biology that are of relevance for the research question addressed. In addition, animal models are still regarded as the gold-standard in the context of bone biology and pathology, especially for the development of novel treatment strategies. However, species-specific differences impede the translation of findings from animal models to humans. The current review summarizes and discusses the latest developments in bone tissue engineering and organoid culture including suitable cell sources, extracellular matrices and microfluidic bioreactor systems. With available technology in mind, a best possible bone model will be hypothesized. Furthermore, the future need and application of such a complex model will be discussed.

4.
Genes (Basel) ; 8(10)2017 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-29019963

RESUMO

In the early days of pharmacy, the development of new drugs was frequently achieved by restless chemists who worked solitarily, day by day for years [...].

5.
Genes (Basel) ; 8(10)2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28953246

RESUMO

Air quality depends on the various gases and particles present in it. Both natural phenomena and human activities affect the cleanliness of air. In the last decade, many countries experienced an unprecedented industrial growth, resulting in changing air quality values, and correspondingly, affecting our life quality. Air quality can be accessed by employing microchips that qualitatively and quantitatively determine the present gases and dust particles. The so-called particular matter 2.5 (PM2.5) values are of high importance, as such small particles can penetrate the human lung barrier and enter the blood system. There are cancer cases related to many air pollutants, and especially to PM2.5, contributing to exploding costs within the healthcare system. We focus on various current and potential future air pollutants, and propose solutions on how to protect our health against such dangerous substances. Recent developments in the Organ-on-Chip (OoC) technology can be used to study air pollution as well. OoC allows determination of pollutant toxicity and speeds up the development of novel pharmaceutical drugs.

6.
Nanomedicine ; 13(8): 2415-2423, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28821464

RESUMO

Porous tantalum components are widely used for complex acetabular reconstructions in revision hip arthroplasty. Multiple other metal alloys such as titanium-aluminum-vanadium or cobalt-chromium-molybdenum are principally used in artificial joint setups. We report a case of tantalum component failure being both cause and effect of a multiple metal exposure. Our aims were to assess and to characterize associated particle exposure and biological consequences. Metal level quantification revealed substantial in vivo exposure to particulate and dissociated tantalum, zirconium, chromium, cobalt, molybdenum, titanium, aluminum and vanadium in periprosthetic compartments. Aside from micron-sized particles, nanoparticles of a broad size range and elemental composition were obtained. Histological exams verified a spectrum of necrotic changes in the periprosthetic tissues. In the presented case tantalum release was accompanied by concomitance of particles originating from other utilized metals. We conclude that an overall in vivo exposure assessment is mandatory for realistic appraisal of metal toxicity and associated risks.


Assuntos
Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Falha de Prótese/efeitos adversos , Tantálio/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/patologia , Tamanho da Partícula
7.
Biomaterials ; 98: 31-40, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27179133

RESUMO

In hip arthroplasty the implants' articulating surfaces can be made of a cobalt-chromium-molybdenum (CoCrMo) alloy. The use of these metal-on-metal (MoM) pairings can lead to the release of wear products such as metallic particles and dissociated metal species, raising concerns regarding their safety amongst orthopedic surgeons and the public. MoM-wear particles are reported to be heterogeneous in their physicochemical properties, are capable of inducing adverse effects on a cellular level and are thought to be involved in relevant clinical problems like aseptic osteolysis. Yet, it remains elusive how MoM-wear affects bone forming cells and their progenitors: bone marrow residing mesenchymal stromal cells (MSCs). This study introduces an assessment of the in vivo exposure to particulate and dissociated Co and Cr and evaluates the effects of MoM-wear on MSCs. The exposure to MoM-wear products in vivo and in vitro leads to a decrease in MSCs' osteogenic matrix mineralization and alkaline phosphatase activity on a cellular and systemic level. In conclusion, MoM-wear products are released in the periprosthetic region and elevate bone marrow Co and Cr concentrations towards levels that impair osteogenic differentiation of MSCs. Therefore, the ongoing use of CoCrMo alloys for articulating surfaces in joint replacement implants needs critical reconsideration.


Assuntos
Prótese de Quadril/efeitos adversos , Células-Tronco Mesenquimais/metabolismo , Próteses Articulares Metal-Metal/efeitos adversos , Material Particulado/efeitos adversos , Idoso , Fosfatase Alcalina/sangue , Matriz Óssea/metabolismo , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , Minerais/metabolismo , Osteogênese
8.
Nanomedicine (Lond) ; 10(14): 2139-51, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26214354

RESUMO

AIMS: First, it will be investigated if amino-polyvinyl alcohol-coated superparamagnetic iron oxide nanoparticles (A-PVA-SPIONs) are suitable for MRI contrast enhancement in bone marrow. Second, the impact of A-PVA-SPION exposure in vivo on the viability and key functions of local bone marrow stromal cells (BMSCs) will be investigated. MATERIAL & METHODS: Animals were systemically injected with A-PVA-SPIONs, followed by a 7-day survival time. Accumulation of A-PVA-SPIONs was confirmed by MRI, histology and inductively coupled plasma optical emission spectrometry. BMSCs were isolated from bone marrow for in vitro assessment of their viability and regenerative key functions. RESULTS: In this study, A-PVA-SPIONs were found to accumulate in bone marrow and increase the BMSCs' metabolic activity and migration rate. CONCLUSION: A-PVA-SPIONs appear suitable for contrast enhancement in bone marrow while our data suggest an influence on the BMSCs biology that necessitates future research.


Assuntos
Medula Óssea/metabolismo , Compostos Férricos/química , Células-Tronco Mesenquimais/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Álcool de Polivinil/química , Animais , Meios de Contraste/química , Meios de Contraste/metabolismo , Ratos
9.
Small ; 10(21): 4340-51, 2014 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-24990430

RESUMO

Mesenchymal stromal cells (MSCs) are promising candidates in regenerative cell-therapies. However, optimizing their number and route of delivery remains a critical issue, which can be addressed by monitoring the MSCs' bio-distribution in vivo using super-paramagnetic iron-oxide nanoparticles (SPIONs). In this study, amino-polyvinyl alcohol coated (A-PVA) SPIONs are introduced for cell-labeling and visualization by magnetic resonance imaging (MRI) of human MSCs. Size and surface charge of A-PVA-SPIONs differ depending on their solvent. Under MSC-labeling conditions, A-PVA-SPIONs have a hydrodynamic diameter of 42 ± 2 nm and a negative Zeta potential of 25 ± 5 mV, which enable efficient internalization by MSCs without the need to use transfection agents. Transmission X-ray microscopy localizes A-PVA-SPIONs in intracellular vesicles and as cytosolic single particles. After identifying non-interfering cell-assays and determining the delivered and cellular dose, in addition to the administered dose, A-PVA-SPIONs are found to be non-toxic to MSCs and non-destructive towards their multi-lineage differentiation potential. Surprisingly, MSC migration is increased. In MRI, A-PVA-SPION-labeled MSCs are successfully visualized in vitro and in vivo. In conclusion, A-PVA-SPIONs have no unfavorable influences on MSCs, although it becomes evident how sensitive their functional behavior is towards SPION-labeling. And A-PVA-SPIONs allow MSC-monitoring in vivo.


Assuntos
Rastreamento de Células/métodos , Dextranos/química , Imagem por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais/citologia , Álcool de Polivinil/química , Idoso , Animais , Diferenciação Celular , Rastreamento de Células/instrumentação , Células Cultivadas , Meios de Contraste/química , Dextranos/síntese química , Feminino , Humanos , Imagem por Ressonância Magnética/instrumentação , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Ratos , Ratos Endogâmicos Lew
10.
Appl Opt ; 52(8): 1655-62, 2013 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-23478769

RESUMO

We present a method for producing monolithically integrated complementary metal-oxide-semiconductor (CMOS) optical filters with different and customer-specific responses. The filters are constituted by a Fabry-Perot resonator formed by two Bragg mirrors separated by a patterned cavity. The filter response can be tuned by changing the geometric parameters of the patterning, and consequently the cavity effective refractive index. In this way, many different filters can be produced at once on a single chip, allowing multichanneling. The filter has been designed, produced, and characterized. The results for a chip with 24 filters are presented.

11.
Hum Pathol ; 38(4): 668-72, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17367608

RESUMO

Diagnosis of primary spindle cell tumors of the spleen is challenging because of the limited immunologic and cytogenetic characterization of this rare entity. We report a case of primary follicular dendritic cell (FDC) sarcoma of the spleen in a 44-year-old woman. Indications for FDC included positive staining for CD21, Ki-M4P, CD14, and fascin. Expression of both standard FDC markers CD23 and CD35 was detected immunohistochemically using tyramide signal amplification. Cytogenetic analysis revealed multiple clonal chromosomal aberrations involving unbalanced translocations of chromosomes X, 3, 5, 7, 8, 9, and 10, leading to net gains at 3q, 7p, 8q, and 9q and net losses at Xp, 8p, 9p, and 10p. Loss at Xp has been described previously in another tumor with FDC features, suggesting that this aberration might play a common role in this malignancy.


Assuntos
Sarcoma/patologia , Neoplasias Esplênicas/patologia , Adulto , Aberrações Cromossômicas , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 5/genética , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 8/genética , Cromossomos Humanos Par 9/genética , Cromossomos Humanos X/genética , Células Dendríticas Foliculares/patologia , Evolução Fatal , Feminino , Humanos , Receptores de Complemento 3b/análise , Receptores de IgE/análise , Sarcoma/genética , Neoplasias Esplênicas/genética , Translocação Genética
12.
J Clin Microbiol ; 44(6): 2019-24, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16757592

RESUMO

The species Campylobacter fetus is divided into the subspecies C. fetus subsp. venerealis and C. fetus subsp. fetus, which differ in their epidemiologies and clinical importance. The differences between these subspecies make accurate distinction between the two essential. First, the value of seven key tests for the traditional differentiation of C. fetus was investigated. Afterwards, the results of the phenotypic differentiation and PCR were compared to address the question of the reliability of this PCR assay. Altogether, 103 C. fetus isolates were investigated, including the type strains of C. fetus subsp. fetus and C. fetus subsp. venerealis. Depending on the result of the glycine tolerance test, the isolates could be separated into 81 C. fetus subsp. venerealis isolates (glycine intolerant) and 22 C. fetus subsp. fetus isolates (glycine tolerant). For all C. fetus subsp. venerealis strains tested, the results of the selenite reduction assay and sensitivity to metronidazole and cefoperazone completely agreed with the results of the glycine tolerance test (correspondence, 100%). Seventy-three C. fetus subsp. venerealis isolates did not grow at 42 degrees C (correspondence, 90.1%), but eight isolates showed a faintly discernible, flat, dark gray growth. For 22 C. fetus subsp. fetus isolates, the results of additional phenotypic tests only partly agreed with the results of the glycine tolerance test. For C. fetus subsp. fetus the results of the glycine tolerance test showed a relatively good correspondence with those of the selenite reduction assay (correspondence, 81.8%), assays for cefoperazone resistance (correspondence, 86.4%), and assays for growth at 42 degrees C (correspondence, 81.8%). The results of the glycine tolerance test and PCR completely agreed for the 103 C. fetus isolates tested. We conclude that at present the traditional phenotypic characterization of C. fetus subspecies under strongly defined conditions remains indispensable, but this PCR assay constitutes a valuable adjunctive technique for the confirmation of phenotypic results.


Assuntos
Técnicas de Tipagem Bacteriana , Infecções por Campylobacter/veterinária , Campylobacter fetus/classificação , Doenças dos Bovinos/microbiologia , Reação em Cadeia da Polimerase/métodos , Animais , Infecções por Campylobacter/microbiologia , Campylobacter fetus/efeitos dos fármacos , Campylobacter fetus/genética , Bovinos , Meios de Cultura , DNA Bacteriano/análise , Feminino , Glicina/farmacologia , Fenótipo , Selenito de Sódio/metabolismo , Especificidade da Espécie
13.
Berl Munch Tierarztl Wochenschr ; 118(5-6): 186-204, 2005.
Artigo em Alemão | MEDLINE | ID: mdl-15918483

RESUMO

The use of conventional battery cages for hens will be prohibited in Germany in 2007. Only few studies, however, have considered the differences between battery cages and alternative systems with regard to infectious diseases. The existing gaps in the current knowledge need to be closed by research and measures must be developed that will prevent the spread of viral, bacterial, and parasitic infections in alternative poultry housing systems. With regard to virus infections, avian influenza requires particular attention. Since wild birds, particularly anseriformes, represent a reservoir for avian influenza viruses, free-ranging poultry is much more at risk of infection than birds in closed hen-houses. Appropriate measures must prevent direct contact with wild birds and transmission via contaminated water, feed, or equipment. Several bacterial infections of poultry represent zoonoses. Salmonella and Campylobacter are considered as particularly important. To avoid a potential increase in the risk of infection for consumers due to poultry keeping systems that might favour infections with bacterial zoonotic agents, there is a special need for research in this area. With regard to parasitic infections, coccidioses may cause problems in alternative poultry housing systems, and lead to considerable economic consequences. The epidemiological situation concerning infections with Histomonas meleagridis needs to be analysed. Since all compounds that had been used for prophylactic or therapeutic purposes in the past have been banned, there is a need to develop new drugs which are safe for animals and humans.


Assuntos
Galinhas/fisiologia , Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis/veterinária , Abrigo para Animais/normas , Doenças das Aves Domésticas/prevenção & controle , Bem-Estar do Animal , Animais , Controle de Doenças Transmissíveis/normas , Doenças Transmissíveis/transmissão , Feminino , Alemanha , Humanos , Masculino , Zoonoses
14.
ALTEX ; 15(5): 53-56, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-11178542

RESUMO

The aim of our study was to investigate if a cell culture assay can replace the toxin neutralisation test in mice for the potency testing of alpha toxoid containing clostridial vaccines for veterinary use. The basis for the development of our cell culture assay was the detection of the cytotoxic/cytopathic action of alpha toxin on cells in culture. Nine permanent cell lines were examined for their reaction to the alpha toxin. The action of the toxin was determined after three days by microscopic examination and MTT assay. The alpha toxin exhibited the strongest effect on the ESH-L cells. We were able to show that the cytopathic effect was neutralised by the international standard for gas gangrene antitoxin (C.novyi) but never by heterologous antisera. Our results showed that the ESH-L cell line was a suitable indicator for the detection of the cytotoxic effect of alpha toxin.

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