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This chapter deals with type 2 diabetes in vivo models and techniques suitable for testing new anti-diabetic compounds. In particular, the testing of TRP antagonist for beneficial effects against type 2 diabetes is considered. There are many choices of both in vitro techniques and in vivo mode ...

The incidence of autoimmune diabetes has been steadily increasing in the developed world. A complex interplay between genetic factors and dysregulated immune cells ultimately results in breakdown of self-tolerance against islet beta cell antigens and loss of beta cell mass, which le ...

Hair follicle organ culture allows individual hair follicles from many species to be maintained in culture during which time hair fiber is produced. Cultured hair follicles can be used to investigate the role of hair growth regulatory factors especially with regards hair growth stimula ...

Pharmacodynamic modeling is based on a quantitative integration of pharmacokinetics, pharmacological systems, and (patho-) physiological processes for understanding the intensity and time-course of drug effects on the body. Application of such models to the analysis of meani ...

Chemical risk assessment for human health requires a multidisciplinary approach through four steps: hazard identification and characterization, exposure assessment, and risk characterization. Hazard identification and characterization aim to identify the metabol ...

Interspecies extrapolation encompasses two related but distinct topic areas that are germane to quantitative extrapolation and hence computational toxicology—dose scaling and parameter scaling. Dose scaling is the process of converting a dose determined in an experimental ...

Physiologically based pharmacokinetic (PBPK) models differ from conventional compartmental pharmacokinetic models in that they are based to a large extent on the actual physiology of the organism. The application of pharmacokinetics to toxicology or risk assessment requires ...

Compartmental models are composed of sets of interconnected mixing chambers or stirred tanks. Each component of the system is considered to be homogeneous, instantly mixed, with uniform concentration. The state variables are concentrations or molar amounts of chemical species. Ch ...

When analyzing pharmacokinetic data, one generally employs either model fitting using nonlinear regression analysis or non-compartmental analysis techniques (NCA). The method one actually employs depends on what is required from the analysis. If the primary requirement is to de ...

The human pregnane X receptor (PXR) is a ligand dependent transcription factor that can be activated by structurally diverse agonists including steroid hormones, bile acids, herbal drugs, and prescription medications. PXR regulates the transcription of several genes involved in x ...

In silico tools specifically developed for prediction of pharmacokinetic parameters are of particular interest to pharmaceutical industry because of the high potential of discarding inappropriate molecules during an early stage of drug development itself with consequent s ...

Absorption takes place when a compound enters an organism, which occurs as soon as the molecules enter the first cellular bilayer(s) in the tissue(s) to which is it exposed. At that point, the compound is no longer part of the environment (which includes the alimentary canal for oral exposure), but has be ...

In clinical toxicology, a better understanding of the pharmacokinetics of the drugs may be useful in both risk assessment and formulating treatment guidelines for patients. Pharmacokinetics describes the time course of drug concentrations and is a driver for the time course of drug effe ...

Chemical compounds participate in all the processes of life. Understanding the complex interactions of small molecules such as metabolites and drugs and the biological macromolecules that consume and produce them is key to gaining a wider understanding in a systemic context. Chemical ...

Efficient storage and retrieval of chemical structures is one of the most important prerequisite for solving any computational-based problem in life sciences. Several resources including research publications, text books, and articles are available on chemical structure rep ...

Computational molecular models of chemicals interacting with biomolecular targets provides toxicologists a valuable, affordable, and sustainable source of in silico molecular level information that augments, enriches, and complements in vitro and in vivo efforts. From a mol ...

Physicochemical properties are key factors in controlling the interactions of xenobiotics with living organisms. Computational approaches to toxicity prediction therefore generally rely to a very large extent on the physicochemical properties of the query compounds. Cons ...

Molecular dynamics (MD) simulation holds the promise of revealing the mechanisms of biological processes in their ultimate detail. It is carried out by computing the interaction forces acting on each atom and then propagating the velocities and positions of the atoms by numerical integr ...

Toxicity data is expensive to generate, is increasingly seen as precompetitive, and is frequently used for the generation of computational models in a discipline known as computational toxicology. Repositories of chemical property data are valuable for supporting computation ...

Mathematical modeling is a vehicle that allows for explanation and prediction of natural phenomena. In this chapter we present guidelines and best practices for developing and implementing mathematical models, using cancer growth, chemotherapy, and immunotherapy modeling as e ...