The nation’s leading causes of death are related to alcohol and drug use, tobacco smoke exposure, and behavioral addictions. In addition, the comorbidity of addictions and psychiatric illnesses (ie, dual diagnosis) is… Read More
OBJECTIVE: A three-week in-unit, placebo-controlled, double-blind clinical trial in non-treatment-seeking heroin addicts was undertaken to test the translatability of pre-clinical findings of enhanced opioid analgesia and reduced dependence and tolerance with concomitant ibudilast exposure.
BACKGROUND: Previous animal studies have established that systemic ibudilast administration can improve the analgesic potency and efficacy of therapeutic doses of opioids such as morphine and oxy
Advertisement. Search. Still not a subscriber to JACC Imaging or JACC Interventions? J Am Coll Cardiol, 2012; 59: 2221-2305, doi: 10.1016/j.jacc.2012.02.010 ( Published online 8 May 2012). 2012 by the American College of Cardiology Foundation.
Chemokine (C-C motif) ligand 2, also known as monocyte chemoattractant protein 1 (MCP-1) is an important factor for the pathogenesis of HIV-associated neurocognitive disorders (HAND). The mechanisms of MCP-1-mediated neuropathogenesis, in part, revolve around its neuroinflammatory role and the recruitment of monocytes into the central nervous system (CNS) via the disrupted blood-brain barrier (BBB). We have previously demonstrated that HIV-1/HIV-1 Tat upregulate platelet-derived growth factor (PDGF)-BB, a
Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype.|Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Leve
Cerebral blood flow (CBF) is known to be dysregulated in persons with human immunodeficiency virus 1 (HIV-1), for uncertain reasons. This is an important issue because impaired vasoreactivity has been associated with increased risk of ischemic stroke, elevated overall cardiovascular risk and cognitive impairment.|Cerebral blood flow (CBF) is known to be dysregulated in persons with human immunodeficiency virus 1 (HIV-1), for uncertain reasons. This is an important issue because impaired vasoreactivity has
Opiate addiction is characterized by drug tolerance and dependence which involve adaptive changes in -opioid receptors (MORs) signaling. Regulators of G-protein signaling RGS9, RGS4 and RGS10 proteins negatively regulate G(i/o) protein activity modulating MOR function. An important role of RGS proteins in drug addiction has been described but the status of RGS proteins in human brain of opiate addicts remains unknown. The present study evaluated the immunoreactivity levels of RGS4, RGS9 and RGS10 proteins in prefrontal cortex of short- (n = 15) and long-term (n = 21) opiate abusers and in matched control subjects. RGS4 protein was not altered in short-term opiate abusers but, in long-term abusers it was significantly up-regulated ( = 29 6%). RGS10 protein expression was significantly decreased in short-term ( = -42 7%) but remained unaltered in long-term opiate abusers. RGS9 protein levels in opiate abusers did not differ from matched controls either in the short-term or
INTRODUCTION: Single opioid analgesics are modestly effective in reducing pain but have a narrow therapeutic index and frequently produce intolerable side effects. Adjuvant analgesics are often used to improve the opioid therapeutic index. Basic science research has accumulated evidence that opioid combinations in animal models and in vitro have potential to improve the therapeutic index of opioids and/or prevent opioid tolerance. AREAS COVERED: Opioid receptor pharmacology is reviewed including receptor genetics and downstream signaling. Receptor functional selectivity and ligand biased responses are discussed in relationship to opioid pharmacodynamics, signal modulation and synergy. The accumulated bench research over the past decade, in particular, provides a rationale for considering clinical trials of opioid combinations. These combinations include both selective agonist-agonist or agonist-antagonist pairs which are reviewed. EXPERT OPINION: The use of opioid antagonists
The -opioid receptors mainly contribute to the control of pain transmission, while a number of splice variants may have different physiological roles. In fact, some -opioid receptor agonists show distinct antinociceptive properties probably mediated via splice variants insensitive to traditional -opioid receptor agonists. These atypical -opioid receptor agonists are extremely effective against morphine-resistant interactive pain and lack the psychological dependence liability. -Opioid receptor splice variants specific for these atypical agonists may be the target for better analgesics effective against morphine-resistant interactive pain and lacking psychological dependence liability.
The analgesic effect of codeine depends on the formation of the opioid metabolites morphine and morphine-6-glucuronide. Different factors have been shown or suspected to affect the safety and efficacy of codeine treatment. The objective of the current study is to assess and quantify the impact of important pharmacokinetic factors, using a mechanistic modeling approach.|By means of a generic modeling approach integrating prior physiologic knowledge, we systematically investigated the complex dependence of opioid exposure on cytochrome P450 2D6 and 3A4 (CYP2D6 and CYP3A4), and uridine diphosphate glucuronosyltransferase 2B7 (UGT2B7) activity, as well as renal function, by means of a virtual clinical trial.|First, the known dominant role of CYP2D6 activity for morphine exposure was reproduced. Second, the model demonstrated that mild and moderate renal impairment and co-administration of CYP3A4 inhibitors have only minor influences on opioid exposure. Third, the model showed - in
Forskolin (7beta-acetoxy-1alpha,6beta,9alpha-trihydroxy-8,13-epoxy-labd-14-en-11-one) is the first main labdane diterpenoid isolated from the roots of the Indian Plectranthus barbatus ANDREWS and one of the most extensively studied constituents of this plant. The unique character of forskolin as a general direct, rapid and reversible activator of adenylyl cyclase not only underlies its wide range of pharmacological effects but also renders it as a valuable tool in the study of the role of cAMP. The purpose of this review is to provide data presenting the utility of forskolin--as a cAMP activator--for studying the function of cAMP from different biological viewpoints as follows: 1) Investigation on the role of cAMP in various cellular processes in different organs such as gastrointestinal tract, respiratory tract, reproductive organs, endocrine system, urinary system, olfactory system, nervous system, platelet aggregating system, skin, bones, eyes, and smooth muscles. 2) Studies on the
APRIL JOGC AVRIL 2011 l 367 Substance Use in Pregnancy This clinical practice guideline has been prepared by the Working Group on Problematic Substance Use in Pregnancy, reviewed by the Maternal Fetal Medicine Committee, the Family Physicians
Five Steps to Improving Patient Access Judy Capko, May 21, 2013 Patient access is getting increased attention through reform initiatives. Here are five steps you can take to make sure patients get appropriate access to care in your office.