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Novel Opioid

Cheryl A Thompson
No abstract text is available yet for this article.
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
Lu Cao, Mingui Fu, Santosh Kumar, Anil Kumar
Methamphetamine (METH), a commonly used controlled substance, is known to exacerbate neuropathological dysfunction in HIV-infected individuals. The neuropathological manifestation results from cell death or dysfunction in the central nervous system (CNS) wherein autophagy is expected to have an important role. Autophagy is generally considered protective during deprivation/stress. However, excessive autophagy can be destructive, leading to autophagic cell death. This study was designed to investigate if METH and HIV-1 gp120 interact to induce autophagy in SVGA astrocytes, and whether autophagy is epiphenomenal or it has a role in METH- and gp120-induced cytotoxicity...
October 20, 2016: Cell Death & Disease
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
Giorgia Macedonio, Azzurra Stefanucci, Cristina Maccallini, Sako Mirzaie, Ettore Novellino, Adriano Mollica
The endocannabinoid system is activated by the binding of natural arachidonic acid derivatives (endogenous cannabinoids or endocannabinoids) as lipophilic messengers to cannabinoid receptors CB1 and CB2. The endocannabinoid system comprises also many hydrolytic enzymes responsible for the endocannabinoids cleavage, such as FAAH and MAGL. These two enzymes are possible therapeutic targets for the development of new drugs as indirect cannabinoid agonists. Recently a new family of endocannabinoid modulators was discovered; the lead of this family is the nonapeptide hemopressin produced from enzymatic cleavage of the α-chain of hemoglobin and acting as negative allosteric modulator of CB1...
October 7, 2016: Protein and Peptide Letters
H D Rashmi, H K Komala
BACKGROUND: The procedures in anesthesia such as laryngoscopy and endotracheal intubation are the most important skills to be mastered by an anesthesiologist. However, they produce marked cardiovascular responses such as hypertension and tachycardia. Various drugs have been used to suppress this response. One of those is a novel centrally acting α2 agonist - dexmedetomidine. It has numerous uses in anesthesia as it is having sedative, analgesic, hypnotic, and opioid sparing effects. It is also known to suppress the hemodynamic response to laryngoscopy and intubation...
September 2016: Anesthesia, Essays and Researches
Scott N Lucyk, Lewis S Nelson
No abstract text is available yet for this article.
October 10, 2016: Annals of Emergency Medicine
Tyler A Johnson, Laura Milan-Lobo, Tao Che, Madeline Ferwerda, Eptisam Lambo, Nicole L McIntosh, Fei Li, Li He, Nicholas Lorig-Roach, Phillip Crews, Jennifer Lynne Whistler
Opioid therapeutics are excellent analgesics, whose utility is compromised by dependence. Morphine (1) and its clinically relevant derivatives such as OxyContin® (4), Vicodin® (5) and Dilaudid® (6) are "biased" agonists at the µ opioid receptor (OR), wherein they engage G-protein signaling but poorly engage β-arrestin and the endocytic machinery. In contrast, the endorphins, met-enkephalin (14) and β-endorphin (15), endogenous peptide agonists for ORs, are more potent analgesics then 1, show reduced liability for tolerance and dependence, and engage both G-protein and β-arrestin pathways as "balanced" agonists...
October 17, 2016: ACS Chemical Neuroscience
Srinu Reddi, Naveen Kumar, Rishika Vij, Sanusi Bello Mada, Suman Kapila, Rajeev Kapila
Milk is a potential nutraceutical with wide range of bioactive compounds that are antioxidative, antimicrobial, antithrombotic, immunomodulatory, opioid and antihypertensive. Various intervention studies with milk reflect its stupendous role in elevating bone mineral density. Milk and milk products have shown a preventive effect in bone loss during pre- and postmenopausal women. Since, milk is proved to have a vital role in bone health promotion, there is a need to identify bioactive compounds within it. Recently we have reported four novel peptides from milk casein for their osteoblast proliferation activity...
September 14, 2016: Journal of Nutritional Biochemistry
Marcin Kunecki, Wojciech Płazak, Tomasz Roleder, Jolanta Biernat, Tomasz Oleksy, Piotr Podolec, Krzysztof Stanisław Gołba
BACKGROUND: Ischemic preconditioning (IPC) and postconditioning (POC) are the novel strategies of attaining cardioprotection against ischemia/reperfusion (I/R) injury. Previous studies suggested the role of opioid pathway, however the class of opioid receptors responsible for this effect in humans remains unknown. The aim of the study was to assess the influence of opioids on simulated I/R injury outcomes in the human myocardium. METHODS: Trabeculae of the human right atrium were electrically driven in organ bath and subjected to simulated I/R injury...
October 13, 2016: Cardiology Journal
Bryan Sakamoto, Shelly Keiser, Russell Meldrum, Gene Harker, Andrew Freese
Importance: Liposomal bupivacaine is a novel extended-duration anesthetic that has recently been used for local infiltration in total knee arthroplasty (TKA). Athough liposomal bupivacaine is widely used, it is unknown if the benefits justify the cost in the veteran population at our institution. Objective: To evaluate a change in practice: the effect of local infiltration of liposomal bupivacaine on perioperative outcomes in patients undergoing primary TKA. Design, Setting, and Participants: A retrospective cohort study was conducted among patients who underwent primary TKA at a Veterans Affairs Medical Center before (March 3, 2013-March 2, 2014) and after (March 3, 2014-March 2, 2015) the implementation of liposomal bupivacaine for local infiltration in TKA...
October 12, 2016: JAMA Surgery
Travis T Wager, Thomas A Chappie, David Horton, Ramalakshmi Y Chandrasekaran, Brian M Samas, Elizabeth Dunn-Sims, Cathleen Hsu, Nawshaba Nawreen, Michelle A Vanase-Frawley, Rebecca E O'Connor, Christopher Schmidt, Keith Dlugolenski, Nancy C Stratman, Mark J Majchrzak, Bethany L Kormos, David Nguyen, Aarti Sawant-Basak, Andy N Mead
Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (≥4/6)...
October 7, 2016: ACS Chemical Neuroscience
Lars Peter Holst Andersen
The hormone, melatonin is produced with circadian rhythm by the pineal gland in humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g. blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune function and anti-oxidative defence. Interestingly, a number of experimental animal studies demonstrate significant dose-dependent anti-nociceptive effects of exogenous melatonin. Similarly, recent experimental- and clinical studies in humans indicate significant analgesic effects...
October 2016: Danish Medical Journal
Jörn Lötsch, Alfred Ultsch
OBJECTIVE: The public accessibility of "big data" about the molecular targets of drugs and the biological functions of genes allows novel data science-based approaches to pharmacology that link drugs directly with their effects on pathophysiologic processes. This provides a phenotypic path to drug discovery and repurposing. This paper compares the performance of a functional genomics-based criterion to the traditional drug target-based classification. METHODS: Knowledge discovery in the DrugBank and Gene Ontology databases allowed the construction of a "drug target versus biological process" matrix as a combination of "drug versus genes" and "genes versus biological processes" matrices...
October 1, 2016: European Journal of Clinical Pharmacology
Andrew C Eppstein, Bryan Sakamoto
Opioids are important for surgical pain control but may not be appropriate for patients with narcotic abuse histories or opioid intolerance. We describe a laparoscopic bilateral inguinal herniorrhaphy performed without perioperative or postoperative narcotics. Postoperative analgesia involves a novel technique using 2 different bupivacaine formulations that act synergistically to avoid lag time and provide extended pain relief during the acute surgical recovery phase.
November 2016: Journal of Clinical Anesthesia
Raphael Jorand, Sunetra Biswas, Devin L Wakefield, Steven J Tobin, Ottavia Golfetto, Kelsey Hilton, Michelle Ko, Joe W Ramos, Alexander R Small, Peiguo Chu, Gagandeep Singh, Tijana Jovanovic-Talisman
Pancreatic ductal adenocarcinoma (PDAC), a particularly aggressive malignancy, has been linked to atypical levels, certain mutations, and aberrant signaling of G-protein coupled receptors (GPCRs). GPCRs have been challenging to target in cancer because they organize into complex networks in tumor cells. To dissect such networks with nanometer-scale precision, traditional biochemical approaches were combined herein with super-resolution microscopy methods. A novel interaction specific to PDAC was identified between mu opioid receptor (MOR) and somatostatin receptor 2 (SSTR2)...
September 28, 2016: Molecular Biology of the Cell
Ahmed H Othman, Ahmad M Abd El-Rahman, Fatma El Sherif
BACKGROUND: Breast surgery is an exceedingly common procedure with an increased incidence of acute and chronic pain. Pectoral nerve block is a novel peripheral nerve block alternative to neuro-axial and paravertebral blocks for ambulatory breast surgeries. OBJECTIVES: This study aims to compare the analgesic efficacy and safety of modified Pecs block with ketamine plus bupivacaine versus bupivacaine in patients undergoing breast cancer surgery. STUDY DESIGN: A randomized, double-blind, prospective study...
September 2016: Pain Physician
James Dodington, Pina Violano, Carl R Baum, Kirsten Bechtel
Significant breakthroughs in the field of injury prevention and childhood safety have occurred during the past half-century. For example, the Poison Prevention Packaging Act of 1970 and the institution of child passenger safety laws are responsible for a significant reduction in injuries among children and adolescents. This review will focus on the following three topics because of their significant contribution to pediatric injury morbidity, especially among adolescents, and their promise for further effective prevention research...
September 27, 2016: Pediatric Research
Dennis Gacigi Kinuthia, Anne W Muriithi, Peter Waweru Mwangi
ETHNOPHARMACOLOGICAL RELEVANCE OF THE STUDY: Diarrhea remains one of the main killers of children aged below five years. Traditional antidiarrheal remedies form a potentially viable source of novel low cost efficacious treatments in low resource settings. There is therefore a pressing need to scientifically evaluate these remedies. AIM OF THE STUDY: This study aimed to investigate the in vivo and in vitro antidiarrheal activity of freeze dried Bidens biternata, a herb used in traditional Ayurvedic medicine in the management of diarrhea...
September 21, 2016: Journal of Ethnopharmacology
Lynn R Webster, Carmela Pantaleon, Manish S Shah, Ray DiFalco, Matthew Iverson, Michael D Smith, Eric R Kinzler, Stefan Aigner
OBJECTIVE:  Misuse and abuse of prescription opioids remains a major healthcare concern despite considerable efforts to increase public awareness. Abuse-deterrent formulations of prescription opioids are designed to reduce intentional misuse, abuse, and prescription opioid-related death. A novel extended-release (ER) formulation of morphine (Morphine ARER; MorphaBond™) resists physical manipulation and retains the drug's ER characteristics, even if attempts are made to manipulate the formulation...
September 20, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Ayesha Sajid, Aaron Whiteman, Richard L Bell, Marion S Greene, Eric A Engleman, R Andrew Chambers
BACKGROUND AND OBJECTIVES: Fourfold increases in opioid prescribing and dispensations over 2 decades in the U.S. has paralleled increases in opioid addictions and overdoses, requiring new preventative, diagnostic, and treatment strategies. This study examines Prescription Drug Monitoring Program (PDMP) tracking as a novel measure of opioid addiction treatment outcomes in a university-affiliated integrated mental health-addiction treatment clinic. METHODS: Repeated measure parametrics examined PDMP and urine drug screening (UDS) data before and after first injection for all patients (N = 68) who received at least one long-acting naltrexone injection (380 mg/IM) according to diagnostic groupings of having either (i) alcohol (control); (ii) opioid; or (iii) combined alcohol and opioid use disorders...
October 2016: American Journal on Addictions
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