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The tachykinins represent one of the most thoroughly investigated family of neuropeptides, whose members and receptors have been characterized at the genetic and molecular level and whose pharmacology has now been advanced to the first clinical application. These exciting accomplishments and prospects are reviewed and discussed in this volume in an authoritative manner. Particular emphasis is laid on the development of selective non-peptide antagonists for all 3 tachykinin receptors and their potential as novel drugs in a variety of diseases. The approval of the first tachykinin receptor antagonist as an antiemetic drug is particularly highlighted, and the utility of tachykinin receptor antagonists in affective disorders, chronic obstructive airway disease and irritable bowel syndrome, to name a few indications, is extensively considered.
Hepatitis C virus (HCV) was first identified in 1989 as the etiologic agent of non-A, non-B hepatitis [1] and is currently recognized as the leading cause of chronic liver disease worldwide. In contrast to hepatitis B virus infection, in which only about 5% of adult infections become chronic, more than 80% of HCV-infected patients develop chronic hepatitis. Moreover, 20-50% of those persistently infected with HCV will develop liver cirrhosis and hepatocellu lar carcinoma (HCC) [2]. It is estimated that there are 10,000 deaths in the USA per year due to chronic liver failure or HCC [3]. In addition, HCV dis 25-50% of all liver transplants in US centers, and the ease is responsible for recurrence of HCV infection following liver transplantation is universal [4]. Typically, HCV disease emerges after a 10-20 year period during which symp toms, if they exist at all, are mild and non-specific. Although the prevalence varies greatly among different countries, it has been estimated that up to 170 million people (3% of the world's population), are infected with HCV [5]. A recent study in the USA found that 65% of all HCV-infected persons are 30 to 49 years old [6].
This volume addresses neuronal pain mechanisms at the peripheral, spinal and supraspinal level which are thought to significantly contribute to pain and which may be the basis for the development of new treatment principles. Chapters on nociceptive mechanisms in the peripheral nociceptive system address the concept of hyperalgesic priming, the role of voltage-gated sodium channels in different inflammatory and neuropathic pain states, the hyperalgesic effects of NGF in different tissues and in inflammatory and neuropathic pain states, and the contribution of proteinase activated receptors (PAR) to the development of pain in several chronic pain conditions. Chapters on nociceptive mechanisms in the spinal cord address the particular role of NO and of glial cell activation in the generation and maintenance of inflammatory and neuropathic pain and it discusses the potential role of local inhibitory interneurons, of the endogenous endocannabinoid system and the importance of non-neuronal immune mechanisms in opioid signaling in the control of pain. Furthermore, it is presented how spinal mechanisms contribute to the expression of peripheral inflammation.
The long tube that makes up the gastrointestinal tract is composed of a variety of tissue types and is the largest internal organ of the body. Its main function is to digest food and absorb the released nutrients. Furthermore, it is subdivided into functionally distinct regions that each mediate one of a variety of actions upon the food consumed, i
Overlooked in the early accounts was that all organisms face many additional types of natural challenges and obstacles in their efforts to survive and reproduce: for example, they must fight or escape predators, replenish diminished food supplies, and anticipate, seasonal changes of climate. Weiner's survey of the literature shows that much progress has been made in understanding the effects of exposing animals to these kinds of naturally occurring stressful experiences and their varied outcomes. Under such conditions there appear patterns of integrated behavioral and physiological responses that are exquisitely attuned to the experience. He carefully assesses the research on the ways in which neural circuits and peptidergic mechanisms in the brain generate and integrate these patterns. In addition, he presents new concepts about the perturbation of subsystems, including biological clocks, which may, or may not, lead to disease or ill-health.
High-pressure Molecular Spectroscopy describes examples of the applications of several spectroscopic methods to investigate the behavior of various chemical systems under high pressures, including guest-host interactions, chemical reactions, molecule-based multiferroics, lanthanide ion-doped glasses, and organic, inorganic and organometallic materials. The techniques involved include: Luminescence studies Inelastic neutron scattering Infrared and Raman studies Synchrotron X-ray diffraction
It is now well recognized that the brain, and especially the hypothalamus, plays an important role in the regulation of immune reactions and inflammation. This book aims to review our current state of knowledge of this important field. Key historical findings are presented, and the reciprocal interactions between the brain and the immune system are examined. Particular emphasis is placed on inflammation, a critical host defense reaction that serves as an effector response for both the adaptive and innate immune systems.Mechanisms implicated in brain defense, as well as in more general host defense, are discussed. The regulatory influences of the brain on inflammatory responses are included w...
Neuromodulation will be the first comprehensive and in-depth reference textbook covering all aspects of the rapidly growing field of neuromodulation. This book provides a complete discussion of the fundamental principles of neuromodulation and therapies applied to the brain, spinal cord, peripheral nerves, autonomic nerves and various organs. The textbook is highly structured and organized into overarching sections that cover chronic pain, movement disorders, psychiatric disorders, epilepsy, functional electrical stimulation, cardiac, gastrointestinal, genitourinary and organ neuromodulation. The fundamental principles of electricity and infusion, neural tissue interface, biomedical engineer...