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
In order to summarize current knowledge about the drug "Krokodil" a systematic review including a literature search of the databases PubMed, Embase, Scopus, and Google was conducted in December 2011. According to information acquired, "Krokodil" is a mixture of several substances and was first reported to have been used in Russia in 2003. The core agent of "Krokodil" is desomorphine, an opioid-analogue that can be easily and cheaply manufactured by oneself. Self-production results in a contaminated suspension that is injected intravenously. Due to its pharmacologic features, desomorphine shows a high potential to cause dependence. Against the background of first possible cases of "Krokodil" use in Western Europe, it appears advisable to provide information regarding the fatal consequences of "Krokodil."
We previously identified four missense mutations in the prodynorphin gene that cause human neurodegenerative disorder spinocerebellar ataxia type 23 (SCA23). Three mutations substitute Leu(5), Arg(6), and Arg(9) to Ser (L5S), Trp (R6W) and Cys (R9C) in dynorphin A(1-17) (Dyn A), a peptide with both opioid activities and non-opioid neurodegenerative actions. It has been reported that Dyn A administered intrathecally (i.t.) in femtomolar doses into mice produces nociceptive behaviors consisting of hindlimb scratching along with biting and licking of the hindpaw and tail (SBL responses) through a non-opioid mechanism. We here evaluated the potential of the three mutant peptides to produce similar behaviors. Compared to the wild type (WT)-peptide, the relative potency of Dyn A R6W, L5S and R9C peptides for SBL responses was 50-, 33- and 2-fold higher, and Dyn A R6W and L5S induced the SBL responses at a 10-30-fold lower doses. Dyn A R6W was the most potent peptide. The SBL responses
-opioid receptor (MOR) agonists such as morphine are powerful analgesics used for pain therapy. However, the use of these drugs is limited by their side-effects, which include antinociceptive tolerance and dependence. Earlier studies reported that MOR analgesic tolerance is reduced by blockade of -opioid receptors (DORs) that interact with MORs. Recent studies show that the MOR/DOR interaction in nociceptive afferent neurons in the dorsal root ganglion may contribute to morphine analgesic tolerance. Further analysis of the mechanisms for regulating the trafficking of receptors, ion channels and signaling molecules in nociceptive afferent neurons would help to understand the nociceptive mechanisms and improve pain therapy.
We recently reported that the (2)-adrenoreceptor (AR) ligand allyphenyline (9) significantly enhanced morphine analgesia (due to its (2C)-AR agonism), was devoid of sedative side effects (due to its (2A)-AR antagonism), prevented and reversed morphine tolerance and dependence. To highlight the molecular characteristics compatible with this behaviour and to obtain novel agents potentially useful in chronic pain and opioid addiction management, the allyl group of 9 was replaced by substituents of moderate steric bulk (MR) and positive or negative lipophilic () and electronic () contributions in all the possible combinations. Effective novel (2C)-agonists/(2A)-antagonists (2, 3, 10, 12, and 17) were obtained. This study also demonstrated that contradictory combinations of the physicochemical parameters were similarly able to induce the (2A)-activation. Since we had previously observed that the absolute configuration affected only the potency, but not the functional
Morphine and other opiates are among the most widely prescribed and clinically useful medications for the treatment of chronic pain. However, the applicability of these compounds has been severely hampered by the rapid development of tolerance and physical dependence that typically accompanies their repeated use. A growing body of evidence has implicated the regulated functioning of - opioid receptor heteromers in both the modulation of morphine-mediated antinociception, and in the limitation of undesirable side effects resulting from chronic opiate exposure. Moreover, - heteromers exhibit unique ligand binding characteristics and signaling properties, indicating that pharmacological targeting of the - heteromer may represent a novel therapeutic approach for the management of chronic pain and addiction disorders. Therefore, the present review will attempt to summarize the latest relevant findings regarding the regulation and functional characteristics of 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.