Karen Whalen, Richard Finkle, and Thomas A. Panavelil
Lippincott Illustrated Reviews: Pharmacology, Sixth Edition, is the updated, enhanced version of the student-favorite resource for essentials of medical pharmacology. The first-and-best resource, the Lippincott Illustrated Reviews series features clear, effective writing and hundreds of illustrations for ideal rapid review and the assimilation of complex information. Clear, sequential images present mechanisms of action and focus on showing rather than telling students how drugs work. New edition features:
- All NEW chapters on Drugs of Abuse, Drugs for Obesity, Antihistamines, Drugs for Urologic Disorders, Drugs for Hematopoietic Disorders, Drugs for Dermatological Disorders, and Drugs for Bone Disorders
- Over 380 study questions!
- Nearly 600 annotated, full-color illustrations visually explain complex processes!
- Outline format ideal for concise review and foundational learning
Meningitis is an inflammation of the meninges, the membranes that cover the central nervous system. The most frequent causes of the disease are viruses and bacteria. In the past, the disease was commonly referred to as “brain fever” or “brain inflammation,” and extreme temperatures, sun, rain, mental distress, and other factors were believed to be its potent triggers. By the beginning of the twentieth century, these beliefs faded away in the United States and most western European countries. In contrast, some of these archaic notions persist in Russia, where cold air, draft, wet hair, and failure to cover one's head with a hat during winter are perceived as serious risks for contracting meningitis. These sentiments are reflected in the prose of Solzhenitsyn and other contemporary Russian authors. However, in the fictional literature of the nineteenth century, emotional or intellectual disturbances rather than the wrath of winter were portrayed worldwide as the most frequent cause of brain inflammation. Both physicians and laity blamed nervous breakdown or mental distress for the development of meningitis and the tragic deaths of the eminent Russian writer Gogol, talented poet Nadson, and heir to the Imperial throne Grand Duke Nicholas Romanov. Even in the twentieth century, esteemed Russian artists, including Pasternak, Paustovsky, and Roerich, highlighted this belief. Following the discovery of the infectious nature of meningitis, fictional depictions of the illness changed. While literary accounts of brain inflammation by the realists (e.g., Dostoevsky and Flaubert) were rather imprecise, the descriptions of the course and symptoms of meningitis by the modernists (e.g., Balmont, Hesse, and Huxley) became detailed and recognizable. Typically, the victim of the disease is a boy, and his imminent agony is preceded by immense suffering that devastates his parents. The dreadful experience of seeing children in the merciless clutches of meningitis had a profound personal effect on Maugham, Twain, and Russian philosopher Tikhomirov, changing their spiritual convictions. However, several authors, among them Avseenko, Davydov, Gazdanov, and Shmelyov, created uplifting stories of survival of the affliction. In this chapter, references to meningitis in the medical and fictional literature are explored through a cultural and historical prism, which may help readers to understand how and why this disease has held a special significance in the Russian psyche.
Signaling Mechanisms of Vav3, a Guanine Nucleotide Exchange Factor and Androgen Receptor Coactivator, in Physiology and Prostate Cancer Progression
Leah S. Lyons and Kerry L. Burnstein
The Rho GTPase guanine nucleotide exchange factor (GEF) Vav3 is the third member of the Vavfamily of GEFS and is activated by tyrosine phosphorylation. Through stimulation of Rho GTPaseactivity, Vav3 promotes cell migration, invasion, and other cellular processes. Work from our laboratory first established that Vav3 is upregulated in models of castration-resistant prostate cancer progression and enhances androgen receptor as well as androgen receptor splice variant activity. Recent analysis of clinical specimens supports Vav3 as a potential biomarker of aggressive prostate cancer. Consistent with a role in promoting castration-resistant disease, Vav3 is a versatile enhancer of androgen receptor by both ligand-dependent and ligand-independent mechanisms and as such impacts established pathways of androgen receptor reactivation in advanced prostate cancer. Distinct Vav3 domains and mechanisms participate in ligand-dependent and -independent androgen receptor coactivation. To provide a physiologic context, we review Vav3 actions elucidated by gene knockout studies. This chapter describes the pervasive role of Vav3 in progression of prostate cancer to castration resistance. We discuss the mechanisms by which prostate cancer cells exploit Vav3 signaling to promote androgen receptor activity under different hormonal milieus, which are relevant to clinical prostate cancer. Lastly, we review the data on the emerging role for Vav3 in other cancers ranging from leukemias to gliomas.