Log in to search using one of your social media accounts:

 

Identifying links in the chain: the dynamic coupling of catecholamines, Peptide synthesis, and Peptide release in hypothalamic neuroendocrine neurons.
Abstract Compared to neurons that communicate using synapses, some neuroendocrine neurons release relatively large quantities of peptide into the vasculature to control neuroendocrine function. Maintaining adequate amounts of peptide for release through controlled biosynthesis is therefore critical for their function. But how neuroendocrine-or in fact, any neuropeptide-neurons link appropriate levels of peptide biosynthesis with the action potentials that drive peptide release is unknown. Here, we review possible mechanisms in paraventricular hypothalamic CRH neuroendocrine neurons to coordinate these processes in...
Source: Advances in Pharmacology - September 25, 2013 Category: Drugs & Pharmacology Authors: Watts AG, Khan AM Tags: Adv Pharmacol Source Type: research

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP): A Master Regulator in Central and Peripheral Stress Responses.
Abstract The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is a master regulator of central and peripheral stress responses required to restore and maintain homeostasis. PACAP modulates the hypothalamic-pituitary-adrenal (HPA) axis in response to acute psychogenic but not systemic stressors, through activation of corticotropin-releasing hormone (CRH) release to drive adrenal corticosterone (CORT) output. During direct high-frequency stimulation of the splanchnic nerve that is designed to mimic stress, PACAP regulates adrenomedullary catecholamine secretion. In addition to transmission, PA...
Source: Advances in Pharmacology - September 25, 2013 Category: Drugs & Pharmacology Authors: Mustafa T Tags: Adv Pharmacol Source Type: research

Preface.
PMID: 24054158 [PubMed - in process] (Source: Advances in Pharmacology)
Source: Advances in Pharmacology - September 25, 2013 Category: Drugs & Pharmacology Authors: Eiden LE Tags: Adv Pharmacol Source Type: research

Antiviral agents for herpes simplex virus.
Abstract This review starts with a brief description of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), the clinical diseases they cause, and the continuing clinical need for antiviral chemotherapy. A historical overview describes the progress from the early, rather toxic antivirals to acyclovir (ACV) which led the way for its prodrug, valacyclovir, to penciclovir and its prodrug, famciclovir (FCV). These compounds have been the mainstay of HSV therapy for two decades and have established a remarkable safety record. This review focuses on these compounds, the preclinical studies which reveal potentially impo...
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: Vere Hodge RA, Field HJ Tags: Adv Pharmacol Source Type: research

Nucleotide prodrugs for the treatment of HCV infection.
Abstract The HCV RNA-dependent RNA polymerase is an essential enzyme in HCV viral replication and has been a prominent target in the search for therapies to treat individuals infected with HCV. The development of both nucleoside and nucleotide HCV inhibitors has been pursued because of their potential for showing pangenotypic activity and because of their high barrier to resistance. Even though nucleoside inhibitors were shown to be effective in a clinical setting, their potency limited their effectiveness. The exploitation of prodrug strategies to deliver nucleoside 5'-monophosphates has resulted in the developme...
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: Sofia MJ Tags: Adv Pharmacol Source Type: research

HIV Integrase Inhibitors: 20-Year Landmark and Challenges.
ier Y Abstract Since the discovery of HIV as the cause for AIDS 30 years ago, major progress has been made, including the discovery of drugs that now control the disease. Here, we review the integrase (IN) inhibitors from the discovery of the first compounds 20 years ago to the approval of two highly effective IN strand transfer inhibitors (INSTIs), raltegravir (Isentress) and elvitegravir (Stribild), and the promising clinical activity of dolutegravir. After summarizing the molecular mechanism of action of the INSTIs as interfacial inhibitors, we discuss the remaining challenges. Those include: overcoming resista...
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: Métifiot M, Marchand C, Pommier Y Tags: Adv Pharmacol Source Type: research

Advances in the treatment of varicella-zoster virus infections.
Abstract Varicella-zoster virus (VZV) causes two distinct diseases, varicella (chickenpox) and shingles (herpes zoster). Chickenpox occurs subsequent to primary infection, while herpes zoster (usually associated with aging and immunosuppression) appears as a consequence of reactivation of latent virus. The major complication of shingles is postherpetic neuralgia. Vaccination strategies to prevent varicella or shingles and the current status of antivirals against VZV will be discussed in this chapter. Varivax®, a live-attenuated vaccine, is available for pediatric varicella. Zostavax® is used to boost VZV-s...
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: Andrei G, Snoeck R Tags: Adv Pharmacol Source Type: research

Hepatitis C Virus: Standard-of-Care Treatment.
Abstract Hepatitis C virus (HCV) infection is curable by therapy. The antiviral treatment of chronic hepatitis C has been based for decades on the use of interferon (IFN)-α, combined with ribavirin. More recently, new therapeutic approaches that target essential components of the HCV life cycle have been developed, including direct-acting antiviral (DAA) and host-targeted agents (HTA). A new standard-of-care treatment has been approved in 2011 for patients infected with HCV genotype 1, based on a triple combination of pegylated IFN-α, ribavirin, and either telaprevir or boceprevir, two inhibitors of th...
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: Pawlotsky JM Tags: Adv Pharmacol Source Type: research

Influenza virus resistance to antiviral therapy.
Abstract Antiviral drugs for influenza therapy and prophylaxis are either of the adamantane or neuraminidase inhibitor (NAI) class. However, the NAIs are mainly prescribed nowadays, because of widespread adamantane resistance among influenza A viruses and ineffectiveness of adamantanes against influenza B. Emergence and spread of NAI resistance would further limit our therapeutic options. Taking into account the previous spread of oseltamivir-resistant viruses during the 2007/2008 season preceding the last pandemic, emergence of yet another naturally NAI-resistant influenza virus may not be an unlikely event. This...
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: van der Vries E, Schutten M, Fraaij P, Boucher C, Osterhaus A Tags: Adv Pharmacol Source Type: research

The natural course of chronic hepatitis B virus infection and its management.
Abstract Chronic infection with the hepatitis B virus (HBV) runs a long natural course during which underlying changes in liver histology can progress to cirrhosis and hepatic decompensation, as well as to hepatocellular carcinoma. Therapeutic intervention is currently aiming at suppression of HBV replication by applying a number of pharmacological agents. For an optimum use of available therapies, good knowledge of the natural course of chronic infection, as well as of the role played by several viral, host, and environmental factors, is mandatory. The larger part of this chapter deals with how to treat the vario...
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: Hadziyannis SJ, Vassilopoulos D, Hadziyannis E Tags: Adv Pharmacol Source Type: research

The holý trinity: the acyclic nucleoside phosphonates.
The holý trinity: the acyclic nucleoside phosphonates. Adv Pharmacol. 2013;67:293-316 Authors: De Clercq E Abstract The Holý Trinity was named after Dr Antonín Holý (the Holý Trinity being an Unesco recognized monument in Olomouc, Czech Republic), who together with Dr John C. Martin (Gilead Sciences) and myself pioneered a new class of antiviral agents, the acyclic nucleoside phosphonates. These compounds have revolutionized the antiviral drug field with several drugs that have been approved for the treatment of various DNA virus infections (cidofovir), hepatitis B (adefo...
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: De Clercq E Tags: Adv Pharmacol Source Type: research

The Nucleoside Reverse Transcriptase Inhibitors, Nonnucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors in the Treatment of HIV Infections (AIDS).
Abstract The majority of the drugs currently used for the treatment of HIV infections (AIDS) belong to either of the following three classes: nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). At present, there are 7 NRTIs, 5 NNRTIs, and 10 PIs approved for clinical use. They are discussed from the following viewpoints: (i) chemical formulae; (ii) mechanism of action; (iii) drug combinations; (iv) clinical aspects; (v) preexposure prophylaxis; (vi) prevention of mother-to-child transmission; (vii) their use in children; (viii...
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: De Clercq E Tags: Adv Pharmacol Source Type: research

Preface.
PMID: 23886006 [PubMed - in process] (Source: Advances in Pharmacology)
Source: Advances in Pharmacology - July 29, 2013 Category: Drugs & Pharmacology Authors: De Clercq E Tags: Adv Pharmacol Source Type: research

Redefining approaches to asthma: developing targeted biologic therapies.
Abstract Asthma is a chronic respiratory disorder canonically associated with type 2 airway inflammation as characterized by elevated levels of eosinophils, immunoglobulin E, and cytokines including interleukin (IL) 4, IL5, IL9, and IL13 and tumor necrosis factor (TNF) α. However, mounting evidence has shown that considerable heterogeneity exists in human asthma in terms of the nature and intensity of airway inflammation. While many asthma patients achieve acceptable control of symptoms with standard-of-care therapies such as β(2)-adrenergic agonists and inhaled corticosteroids, a minority remains sympt...
Source: Advances in Pharmacology - February 28, 2013 Category: Drugs & Pharmacology Authors: Arron JR, Scheerens H, Matthews JG Tags: Adv Pharmacol Source Type: research

Protein Therapeutics Targeted at the TNF Superfamily.
Abstract Protein-based drugs with their unequivocal specificity achieved the long sought milestone of selectively disrupting cytokine pathways to alleviate ongoing inflammation. Tumor necrosis factor (TNF), a member of the superfamily of cytokines involved in regulating immune and inflammatory processes, provides an exemplary model of protein therapeutics. Antibody and receptor-based inhibitors of TNF modify inflammation leading to dramatic improvement in patients with certain autoimmune diseases. Collectively, the structure, specificity and valence of these protein-based drugs provide direct evidence that the ess...
Source: Advances in Pharmacology - February 28, 2013 Category: Drugs & Pharmacology Authors: Ware CF Tags: Adv Pharmacol Source Type: research

Immunopharmacology of lipid a mimetics.
Abstract The structural core of bacterial lipopolysaccharide, lipid A, has played a role in medicine since the 1890s when William Coley sought to harness its immunostimulatory properties in the form of a crude bacterial extract. Recent decades have brought remarkable clarity to the structure of lipid A and the multicomponent endotoxin receptor system that evolved to detect it. A range of therapeutically useful versions of lipid A now exists, including preparations of detoxified lipid A, synthetic copies of naturally occurring biological intermediates such as lipid IVa, and synthetic mimetics. These agents are find...
Source: Advances in Pharmacology - February 28, 2013 Category: Drugs & Pharmacology Authors: Bowen WS, Gandhapudi SK, Kolb JP, Mitchell TC Tags: Adv Pharmacol Source Type: research

The Biology of Thymic Stromal Lymphopoietin (TSLP).
Abstract Originally shown to promote the growth and activation of B cells, thymic stromal lymphopoietin (TSLP) is now known to have wide-ranging impacts on both hematopoietic and nonhematopoietic cell lineages, including dendritic cells, basophils, eosinophils, mast cells, CD4(+), CD8(+) and natural killer T cells, B cells and epithelial cells. While TSLP's role in the promotion of TH2 responses has been extensively studied in the context of lung- and skin-specific allergic disorders, it is becoming increasingly clear that TSLP may impact multiple disease states within multiple organ systems, including the blockad...
Source: Advances in Pharmacology - February 28, 2013 Category: Drugs & Pharmacology Authors: Ziegler SF, Roan F, Bell BD, Stoklasek TA, Kitajima M, Han H Tags: Adv Pharmacol Source Type: research

Eicosanoids in metabolic syndrome.
Abstract Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that...
Source: Advances in Pharmacology - February 28, 2013 Category: Drugs & Pharmacology Authors: Hardwick JP, Eckman K, Lee YK, Abdelmegeed MA, Esterle A, Chilian WM, Chiang JY, Song BJ Tags: Adv Pharmacol Source Type: research

The Yin and Yang of Protein Kinase C-theta (PKCθ): A Novel Drug Target for Selective Immunosuppression.
The Yin and Yang of Protein Kinase C-theta (PKCθ): A Novel Drug Target for Selective Immunosuppression. Adv Pharmacol. 2013;66:267-312 Authors: Zhang EY, Kong KF, Altman A Abstract Protein kinase C-theta (PKCθ) is a protein kinase C (PKC) family member expressed predominantly in T lymphocytes, and extensive studies addressing its function have been conducted. PKCθ is the only T cell-expressed PKC that localizes selectively to the center of the immunological synapse (IS) following conventional T cell antigen stimulation, and this unique localization is essential for PKCθ-mediated dow...
Source: Advances in Pharmacology - February 28, 2013 Category: Drugs & Pharmacology Authors: Zhang EY, Kong KF, Altman A Tags: Adv Pharmacol Source Type: research

Preface.
PMID: 23433460 [PubMed - in process] (Source: Advances in Pharmacology)
Source: Advances in Pharmacology - February 28, 2013 Category: Drugs & Pharmacology Authors: Webb DR Tags: Adv Pharmacol Source Type: research