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Transient receptor potential (TRP) channels are abundantly expressed in vascular endothelium where the channels play important functional roles. In this chapter, we describe some well-established approaches, from molecular detection to functional assays, to study the role of T ...

Cardiomyopathy refers to the cardiac remodeling process in response to a variety of intrinsic and extrinsic stimuli that stress the heart. To discover novel therapeutic strategies for the disease, we are establishing and characterizing adult zebrafish models of cardiomyopathy. O ...

Transient receptor potential (TRP) is a large superfamily of cation channels comprising 28 members in mammals. TRP channels are ubiquitously expressed in human tissues, including the cardiovascular system where they have been associated with a number of physiological functions, s ...

Muscular dystrophy is a severe degenerative disorder of the skeletal muscle, characterized by progressive muscle weakness. One subgroup of this disease is caused by a defect in the genes encoding the components of the dystrophin–glycoprotein complex. Such a defect results in a signific ...

Rheumatoid arthritis (RA) is a complex autoimmune disease, with a prevalence of approximately 1% in the population worldwide. RA is a chronic inflammatory disease primarily affecting joints and patients suffer from a plethora of symptoms, including pain, fatigue and stiffness. Joint p ...

Several transient receptor potential (TRP) ion channels are activated by heat and may potentially �contribute to human heat perception though clinical data are currently either limited or absent. At least three of the identified heat-activated TRP channels are appealing drug targe ...

The study of thermonociception in conscious animals is based on the assessment of pain-avoiding behavior from noxious heat or cold stimuli. The conventional tests of heat nociception apply suprathreshold heat stimuli and measure the reflex latency of withdrawal reactions. A novel ap ...

This chapter is devoted to the study of the role of TRP channels in tumorigenesis in vivo using a tumor xenograft model in immunodeficient mice. Either cancerous cells naturally expressing TRP channels, or TRP channel stably expressing cancerous or normal cells, could be injected into immun ...

Inflammatory Bowel Diseases (IBD) are life-threatening chronic and relapsing disorders of the immune system affecting the lower gastrointestinal tract. Despite the considerable efforts of many researchers, much remains to be learnt of their causes and appropriate treatment op ...

This article describes the use of rodent models to evaluate the anti-obesity potential of novel drugs. Although drugs can reduce body weight by altering energy input or energy output, we have focused on the discovery of compounds reducing food intake as this is the most common pharmacological a ...

Animal models of disease are important tools that allow us to model human conditions and test therapies. Metabolic disease, also called the Metabolic Syndrome (MS), is characterized by obesity, insulin resistance (IR), dyslipidemia and hypertension, the simultaneous occurrence of w ...

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 ...