Spectral imaging in preclinical research and clinical pathology.

Spectral imaging methods are attracting increased interest from researchers and practitioners in basic science, pre-clinical and clinical arenas. A combination of better labeling reagents and better optics creates opportunities to detect and measure multiple parameters at the molecular and cellular level. These tools can provide valuable insights into the basic mechanisms of life, and yield diagnostic and prognostic information for clinical applications. There are many multispectral technologies available, each with its own advantages and limitations. This chapter will present an overview of the rationale for spectral imaging, and discuss the hardware, software and sample labeling strategies that can optimize its usefulness in clinical settings

Advanced bioengineering technologies for preclinical research

Current in vitro practices must overcome important challenges to compare favorably with human studies. The limited applicability of conventional in vitro assays and strategies can be explained by the fact that standard approaches do not enable recapitulation of the complexity of human tissues and physiological functions. To address this challenge, novel bioengineering tools, techniques and technologies are rapidly emerging to advance current fundamental knowledge and innovate in vitro practices. For example, organs-on-a-chip have recently appeared as a small-scale solution to overcome the transability, financial and ethical concerns associated with animal studies in drug discovery and development. In parallel, biomimetic interfaces are increasingly recapitulating 3D structures with tissue-like dynamic properties to allow in-depth investigation of disease mechanisms. This review aims at highlighting current bioengineering approaches poised to address the shortcomings of conventional in vitro research practices towards the generation of more effective solutions for improving human health

PRECLINICAL RESEARCH IN HUMAN DRUG DEVELOPMENT

The paper presents the preclinical research requirements according to the legislation in force and it’s implementing guidelines in European Union (EU), tracking down it’s origins to ICH when appropriate. The development of any medicinal product requires its research in terms of quality, safety and efficacy. The new codification system for ICH guidelines adopted by ICH Steering Committee is presented in detail. The five categories of CHMP guidelines are explained. The non-clinical research represents a critical stage for the transition to studies in humans. The paper supports the researchers in their efforts to assess the needs and the timelines in the preclinical research fiel

Guided Tissue Regeneration in Heart Valve Replacement: From Preclinical Research to First-in-Human Trials

Heart valve tissue-guided regeneration aims to offer a functional and viable alternative to current prosthetic replacements. Not requiring previous cell seeding and conditioning in bioreactors, such exceptional tissue engineering approach is a very fascinating translational regenerative strategy. After in vivo implantation, decellularized heart valve scaffolds drive their same repopulation by recipient’s cells for a prospective autologous-like tissue reconstruction, remodeling, and adaptation to the somatic growth of the patient. With such a viability, tissue-guided regenerated conduits can be delivered as off-the-shelf biodevices and possess all the potentialities for a long-lasting resolution of the dramatic inconvenience of heart valve diseases, both in children and in the elderly. A review on preclinical and clinical investigations of this therapeutic concept is provided with evaluation of the issues still to be well deliberated for an effective and safe in-human application

Merck KGAA v. Integra Lifesciences I, Ltd.: Greater Research Protection for Drug Manufacturers

Merck sought protection under a statutory exemption from claims of patent infringement brought by Integra Lifesciences. The Court held unanimously that the safe harbor contained in 35 U.S.C. § 271(e)(1) protected the use of patented inventions used in preclinical research where the results were not submitted to the FDA. The Court\u27s interpretation of the safe harbor provision broadened protection for those engaged in drug research at a substantial cost to patent-holders

Basic and Preclinical Research for Personalized Medicine

Basic and preclinical research founded the progress of personalized medicine by providing a prodigious amount of integrated profiling data and by enabling the development of biomedical applications to be implemented in patient-centered care and cures. If the rapid development of genomics research boosted the birth of personalized medicine, further development in omics technologies has more recently improved our understanding of the functional genome and its relevance in profiling patients\u2019 phenotypes and disorders. Concurrently, the rapid biotechnological advancement in diverse research areas enabled uncovering disease mechanisms and prompted the design of innovative biological treatments tailored to individual patient genotypes and phenotypes. Research in stem cells enabled clarifying their role in tissue degeneration and disease pathogenesis while providing novel tools toward the development of personalized regenerative medicine strategies. Meanwhile, the evolving field of integrated omics technologies ensured translating structural genomics information into actionable knowledge to trace detailed patients\u2019 molecular signatures. Finally, neuroscience research provided invaluable models to identify preclinical stages of brain diseases. This review aims at discussing relevant milestones in the scientific progress of basic and preclinical research areas that have considerably contributed to the personalized medicine revolution by bridging the bench-to-bed gap, focusing on stem cells, omics technologies, and neuroscience fields as paradigms

Preclinical research of the experimental preparation “Ferosel T”

oai:ojs2.ujvas.com.ua:article/1The results of preclinical studies of the new ferrodextran preparation “Ferosel T”, which contains ferrum and selenium, are presented. It has been established that at oral administration of ferrocellus T in a prophylactic dose of 2 ml/kg b.w. and the therapeutic dose of 4 ml/kg for 3 days in a row in the stomach of laboratory rats did not show toxic effects. No toxic effect of T ferrocellus is established at introducing it into the stomach in doses in 3 and 10 times higher than the therapeutic ones. Under conditions of subcutaneous administration of the drug, the death of white rats was not observed, only short-term inhibition of laboratory animals, which was prescribed the drug in a dose of 10 ml/kg b.w. It was established that in the preventive and optimal therapeutic doses the drug did not affect the detoxification function of the liver. In rats, which ferrocellus T was administered at maximum therapeutic and possibly toxic doses, the duration of hexenal sleep was for 32 and 35% higher relative to control values. The investigation of the emotional and behavioral reactions of laboratory animals after administration of ferrocellus T for 21 days in therapeutic and maximum therapeutic doses did not show a significant effect on the nervous system. In terms of hyperemia and swelling of the skin and the thickness of the skin, ferrocellus T in prophylactic and therapeutic doses upon application to rabbit skin did not cause local irritation. Separate injection of the drug “Ferosel T” by sub-planar way to guinea pigs in 0.1 ml. did not cause swollen reactions of the paws. As a result of the conducted research, no allergenic properties of the drug “Ferosel T” were found. In laboratory rats, which were introduced ferrosel T in the prophylactic dose of probable changes in the weight of the heart, liver, spleen and kidneys is not established. In rats, which were administered ferrocellus T in an optimal therapeutic dose, in comparison with control weights of the spleen and liver, respectively, was in 10.3 and 6.4% higher. When introducing ferrocellus T at the maximum therapeutic dose, the mass of the spleen and liver was in 14.0 and 15.0% higher, respectively. The results of the studies indicate that the drug “Ferosel T” is safe when used for the prevention and treatment of animals

Standard operating procedures (SOP) in experimental stroke research: SOP for middle cerebral artery occlusion in the mouse

Recently, systematic reviews have found quantitative evidence that low study quality may have introduced a bias into preclinical stroke research. Monitoring, auditing, and standard operating procedures (SOPs) are already key elements of quality control in randomized clinical trials and will hopefully be widely adopted by preclinical stroke research in the near future. Increasingly, funding bodies and review boards overseeing animal experiments are taking a proactive stance, and demand auditable quality control measures in preclinical research. Every good quality control system is based on its SOPs. This article introduces the concept of quality control and presents for the first time an SOP in experimental stroke research