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 ...
Over the past two decades computational methods have eased up the financial and experimental burden of early drug discovery process. The in silico methods have provided support in terms of databases, data mining of large genomes, network analysis, systems biology on the bioinformatics fr ...
This chapter provides an overview of computational models that describe various aspects of the source-to-health effect continuum. Fate and transport models describe the release, transportation, and transformation of chemicals from sources of emission throughout the general ...
Computational toxicology is a vibrant and rapidly developing discipline that integrates information and data from a variety of sources to develop mathematical and computer-based models to better understand and predict adverse health effects caused by chemicals, such as environ ...
The overactive bladder (OAB) can be defined in humans as a urodynamic observation (detrusor overactivity), or symptomatically (urgency, frequency, incontinence, nocturia) as the OAB syndrome. For obvious reasons, there are no animal models of the OAB syndrome. In humans, urinary incon ...
As in other areas of biomedical research, studies of bladder pathology rely heavily in animal models of cystitis. These can be basically divided in two types: induced by systemically administration and locally induced by challenge with immunogens or irritants. The choice between models is ...
Recently, TRP channels have been implicated in numerous pathologies of the genitourinary (GU) tract. TRP channels are differently expressed along the GU tract, and several lines of evidence suggest that they also have different roles in the pathophysiology of GU tract diseases. In this cha ...
Stimulation of TRP receptors on sensory nerves is likely involved in chemically induced airway symptoms. A subgroup of patients has been identified with nonallergic, nonasthmatic symptoms from the upper and lower airway that are induced by environmental stimuli normally regarded as ...
Under specific pathophysiological circumstances, cough becomes a chronic condition. Unfortunately, apart from drugs that treat the underlying diseases that cause the cough symptom, medicines directly oriented to reduce or abolish the cough reflex are limited to narcotic or narc ...
Lung inflammation models in experimental animals are particularly important to study the mechanisms and complex neuroimmune interactions involved in the pathophysiological processes, to identify key mediators and target molecules, as well as to test novel drug candidates. En ...
Hypoxic pulmonary vasoconstriction (HPV) is an essential physiological mechanism of the lung which matches perfusion to ventilation to optimize gas exchange. Pulmonary arterial smooth muscle cells (PASMC) are the effector and possibly also the sensor cells of HPV. Contraction of th ...
The airways of the lungs are composed of the epithelium, smooth muscle cells, and sensory nerve cells as well as resident immune cells. Transient receptor potential (TRP) channels are expressed in all of these tissues and cells and there is increasing evidence that they play a key role in respiratory ...
The transient receptor potential mucolipin (TRPML) subfamily of transient receptor potential cation channels consists of three members (TRPML1-3) that function at various stages of endocytosis. Conventional research in the TRPML field suggests that dysfunction along these e ...
The perception of temperature is critical in not only acute responses to changes in the environment but also fundamental in regulating homeostatic mechanisms like core body temperature. The somatosensory system detects changes in ambient temperature via the coordinated efforts ...
TRPM7 and its closely related protein TRPM6 are unique bifunctional molecules consisting of a kinase domain fused to an ion channel. The ion channel belongs to the transient receptor potential (TRP) family of ion channels, TRPM subfamily, while the kinase domain belongs to a family of atypical p ...
In this review we summarize the current data on the ion channels TRPM4 and TRPM5. These proteins are to date the only molecular candidates for the class of Ca2+-activated cation channels (CAN channels). They form monovalent cation-selective and Ca-impermeable ion channels, which are activa ...
The TRPM subfamily of transient receptor potential channels includes a number of members which are involved in cell proliferation or cell survival. TRPM2, the second member to be cloned, has a key role in the response to oxidative stress. After exposure to oxidant stress, TNFα, concanavalin A, or a ...
