SPECIAL REQUIREMENTS FOR TOXICOLOGICAL TESTING OF METAL-RELEASING INTRAUTERINE DEVICES

1974 ◽  
Vol 77 (1_Suppla) ◽  
pp. S409-S422 ◽  
Author(s):  
Robert Gordon McConnell
Keyword(s):  
Drug Testing ◽  
Animal Studies ◽  
Intrauterine Devices ◽  
Safety Testing ◽  
Advantages And Disadvantages ◽  
Mutagenicity Assay ◽  
Metal Levels ◽  
History Of ◽  
Animal Safety

ABSTRACT Intrauterine devices (IUD's), intrauterine drug reservoirs (IUDR's), and metal-releasing intrauterine drug reservoirs (MR-IUDR's) with antifertility activity in the animal and human are considered as separate entities. General requirements for toxicologic and teratologic testing of such agents in animals are presented. A comparison reveals the relative advantages and disadvantages of simian, canine, lagomorph, and rodent species. A pretreatment review of obstetric-gynaecologic status and history of each animal is emphasized. Designing of appropriate replicas of the clinical device for use in predictive animal studies requires comparative data on uterine morphology, device-endometrium spatial relationships, and drug release rates. Adult, maternal and foetal tissue metal levels may be important; the analytical methods for detecting and localizing cellular and subcellular wet tissue metal levels are available. Existing in vivo mutagenicity assay procedures are poorly adapted to intrauterine drug testing. Method modifications are explored briefly. A sequence for the animal safety testing of an intrauterine antifertility agent, and its interrelation with clinical research, is outlined.

scholarly journals Iterative Cellular Screening System for Nanoparticle Safety Testing

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Franziska Sambale ◽  
Frank Stahl ◽  
Ferdinand Rüdinger ◽  
Dror Seliktar ◽  
Cornelia Kasper ◽  
...  
Keyword(s):  
Animal Studies ◽  
Titanium Dioxide Nanoparticles ◽  
Three Dimensional ◽  
Good Method ◽  
Screening System ◽  
Human Beings ◽  
Safety Testing ◽  
Mammalian Cell Lines ◽  
Set Up

Nanoparticles have the potential to exhibit risks to human beings and to the environment; due to the wide applications of nanoproducts, extensive risk management must not be neglected. Therefore, we have constructed a cell-based, iterative screening system to examine a variety of nanoproducts concerning their toxicity during development. The sensitivity and application of various cell-based methods were discussed and proven by applying the screening to two different nanoparticles: zinc oxide and titanium dioxide nanoparticles. They were used as benchmarks to set up our methods and to examine their effects on mammalian cell lines. Different biological processes such as cell viability, gene expression of interleukin-8 and heat shock protein 70, as well as morphology changes were investigated. Within our screening system, both nanoparticle suspensions and coatings can be tested. Electric cell impedance measurements revealed to be a good method for online monitoring of cellular behavior. The implementation of three-dimensional cell culture is essential to better mimicin vivoconditions. In conclusion, our screening system is highly efficient, cost minimizing, and reduces the need for animal studies.

scholarly journals Replacement Strategies for Animal Studies in Inhalation Testing

Sci ◽  
2021 ◽  
Vol 3 (4) ◽  
pp. 45
Author(s):  
Eleonore Fröhlich
Keyword(s):  
Animal Models ◽  
In Silico ◽  
Particle Deposition ◽  
Drug Testing ◽  
Animal Studies ◽  
Inhalation Exposure ◽  
Animal Testing ◽  
The Future

Animal testing is mandatory in drug testing and is the gold standard for toxicity and efficacy evaluations. This situation is expected to change in the future as the 3Rs principle, which stands for the replacement, reduction, and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animal testing have increased. The need to develop and use alternatives depends on the complexity of the research topic and also on the extent to which the currently used animal models can mimic human physiology and/or exposure. The lung morphology and physiology of commonly used animal species differs from that of human lungs, and the realistic inhalation exposure of animals is challenging. In vitro and in silico methods can assess important aspects of the in vivo effects, namely particle deposition, dissolution, action at, and permeation through, the respiratory barrier, and pharmacokinetics. This review discusses the limitations of animal models and exposure systems and proposes in vitro and in silico techniques that could, when used together, reduce or even replace animal testing in inhalation testing in the future.

Feasibility of a resorbable anterior cervical graft containment plate

2002 ◽  
Vol 97 (4) ◽  
pp. 440-446 ◽  
Author(s):  
Christopher P. Ames ◽  
G. Bryan Cornwall ◽  
Neil R. Crawford ◽  
Eric Nottmeier ◽  
Robert H. Chamberlain ◽  
...  
Keyword(s):  
Content Type ◽  
Advantages And Disadvantages ◽  
Testing Method ◽  
In Vivo Testing ◽  
History Of ◽  
Cervical Plate ◽  
Cervical Plating ◽  
Design And Testing ◽  
Fine Print

✓ In this article the authors review the history of anterior cervical plating for one- and two-level discectomy for degenerative disease and provide background justification for the design and testing of a cervical plate composed of a resorbable material. The design of the plate is discussed with special reference to modifications of its design and tools compared with metallic plates that are necessary because of the different mechanical properties of the less rigid material. The cadaveric and animal in vivo testing methodologies are described, and a novel testing method for reliably quantifying graft containment is also described. Data from a representative sample are presented. Advantages and disadvantages of resorbable plating are discussed.

scholarly journals Refinement, Reduction, and Replacement (3R) Strategies in Preclinical Testing of Medical Devices

2018 ◽  
Vol 47 (3) ◽  
pp. 329-338 ◽  
Author(s):  
Victoria A. Hampshire ◽  
Samuel H. Gilbert
Keyword(s):  
Drug Administration ◽  
Animal Studies ◽  
Food And Drug Administration ◽  
Large Animal ◽  
Animal Testing ◽  
In Vivo Test ◽  
Scientific Principles ◽  
Radiological Health ◽  
Animal Safety

The U.S. Food and Drug Administration Center for Devices and Radiological Health (FDA/CDRH) has recently published several in vivo test guidance documents that mention refinements, reductions, or replacement animal testing strategies to facilitate the leveraging of data from large animal safety tests for conventional rodent testing. In response to the recently enacted Food and Drug Administration Safety and Innovation Act Section 907, which facilitates expedited access to novel therapies commonly described as Breakthrough Therapy Designation, FDA/CDRH has discussed efficient regulatory strategies for first-in-human investigation, including early feasibility study guidance. Large gains in humane care and translational research could also be attained by examples in FDA’s Guidance for the Use of International Organization for Standardization 10993-1, which states that large animal safety studies may be considered as replacement rodent tests if the scientific principles, methods, and end points (SPME) are considered and applied. This article discusses SPME for the replacement of conventional rodent testing by the inclusion and integration of clinical, diagnostic, and pathologic data obtained from well-designed large animal studies. The recommendations include consideration for study designs that utilize methods for an overall more comprehensive interrogation of animal systems.

scholarly journals Replacement Strategies for Animal Studies in Inhalation Testing

2021 ◽  
Author(s):  
Eleonore Fröhlich
Keyword(s):  
Animal Models ◽  
In Silico ◽  
Particle Deposition ◽  
Drug Testing ◽  
Animal Studies ◽  
Inhalation Exposure ◽  
The Future ◽  
In Silico Models

Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

scholarly journals Polyelectrolyte Multilayer Capsule (PEMC)-Based Scaffolds for Tissue Engineering

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 797
Author(s):  
Georgia Kastania ◽  
Jack Campbell ◽  
Jacob Mitford ◽  
Dmitry Volodkin
Keyword(s):  
Tissue Engineering ◽  
Drug Testing ◽  
Tissue Growth ◽  
Future Perspectives ◽  
Polyelectrolyte Multilayer ◽  
Advantages And Disadvantages ◽  
Cellular Behaviour ◽  
Straightforward Approach

Tissue engineering (TE) is a highly multidisciplinary field that focuses on novel regenerative treatments and seeks to tackle problems relating to tissue growth both in vitro and in vivo. These issues currently involve the replacement and regeneration of defective tissues, as well as drug testing and other related bioapplications. The key approach in TE is to employ artificial structures (scaffolds) to support tissue development; these constructs should be capable of hosting, protecting and releasing bioactives that guide cellular behaviour. A straightforward approach to integrating bioactives into the scaffolds is discussed utilising polyelectrolyte multilayer capsules (PEMCs). Herein, this review illustrates the recent progress in the use of CaCO3 vaterite-templated PEMCs for the fabrication of functional scaffolds for TE applications, including bone TE as one of the main targets of PEMCs. Approaches for PEMC integration into scaffolds is addressed, taking into account the formulation, advantages, and disadvantages of such PEMCs, together with future perspectives of such architectures.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

PERFUSION OF OVARIES IN VITRO AND IN VIVO

1972 ◽  
Vol 68 (2_Supplb) ◽  
pp. S285-S309 ◽  
Author(s):  
Kurt Ahrén ◽  
Per Olof Janson ◽  
Gunnar Selstam
Keyword(s):  
Perfusion System ◽  
Perfusion Technique ◽  
Preliminary Results ◽  
Advantages And Disadvantages

ABSTRACT This paper discusses in vivo and in vitro ovarian perfusion systems described so far in the literature. The interest is not focussed primarily on the results of these studies but rather on the advantages and disadvantages of the techniques and methods used. Another part of the paper summarizes the points which are most important, in our opinion, to take into consideration when developing an in vitro perfusion technique of the ovary. The last part of the paper gives a description of and some preliminary results from an in vitro perfusion system of the rabbit ovary which is under development in this laboratory.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

An overview of Osmotic Drug Delivery System: An update review

2017 ◽  
Vol 6 (7) ◽  
pp. 5426 ◽  
Author(s):  
Hiren J. Patel ◽  
Vaishnavi P. Parikh
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Life Cycle Management ◽  
Delivery Systems ◽  
Osmotic Pump ◽  
Factors Affecting ◽  
Advantages And Disadvantages ◽  
New Chemical Entities ◽  
History Of ◽  
Novel Drug

The pharmaceutical industry has faced several marked challenges in order to bring new chemical entities (NCEs) into the market over the past few decades. Various novel drug delivery approaches have been used as a part of life cycle management from which Osmotic drug delivery systems look the most promising one. After discussing the history of osmotic pump development, this article looks at the principles, advantages and disadvantages of osmotic drug delivery systems. Then, the basic components of osmotic pump and factors affecting the design of oral osmotic drug delivery systems are discussed in detail. In the later part of the manuscript, various types of osmotic pumps available in the market and evaluation methods for osmotic drug delivery systems are discussed in detail.

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