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Sample records for acute morphine treatment

  1. Extended-release morphine sulfate in treatment of severe acute and chronic pain

    PubMed Central

    Balch, Robert J; Trescot, Andrea

    2010-01-01

    Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolism, pharmacodynamics, formulations, and efficacy of the currently available extended-release morphine medications. PMID:21197323

  2. Antinatriuretic effect of acute morphine administration in conscious rats.

    PubMed

    Walker, L A; Murphy, J C

    1984-05-01

    The renal response to the acute administration of morphine was examined in conscious, chronically catheterized, nonhydrated rats. After control clearance periods, morphine sulfate was injected i.v. at 4 mg/kg followed by an infusion of 2 mg/kg X hr. Morphine caused an increase in urine flow which was variable in magnitude and duration. The initial diuresis was not maintained despite continued morphine administration and replacement of lost fluid. Compared to vehicle treatment morphine also induced marked sodium and chloride retention which was sustained throughout the 2-hr infusion period. There were no changes in blood pressure or heart during the clearance periods, although an initial transient hypotension and bradycardia were observed with morphine injection. There were no changes in glomerular filtration rate which could account for the antinatriuresis. Naloxone pretreatment blocked all of the observed renal responses. The results indicate that morphine exerts its effects on electrolyte excretion by enhancing renal tubular sodium or chloride reabsorption rather than changes in systemic hemodynamics or glomerular filtration rate. In a separate series of experiments, urine osmolality, osmolar clearance and free water clearance were estimated. All rats receiving morphine transiently excreted a hypotonic urine (minimum 183 +/- 23 mOsmol/kg of H2O) with a reduction in osmolar clearance and a sharp increase in free water clearance. These findings are consistent with a temporary inhibition of vasopressin release by morphine. PMID:6716265

  3. Effects of Acute and Chronic Morphine on Delay Discounting in Pigeons

    PubMed Central

    Eppolito, Amy K.; France, Charles P.; Gerak, Lisa R.

    2015-01-01

    When reinforcers of different magnitudes are concurrently available, choice is greater for a large reinforcer; that choice can be reduced by delaying its delivery, a phenomenon called delay discounting and represented graphically by a delay curve in which choice is plotted as a function of delay to the large reinforcer. Morphine, administered acutely, can alter responding for large, delayed reinforcers. In this study, the impact of morphine tolerance, dependence and withdrawal on choice of delayed reinforcers was examined in 6 pigeons responding to receive a small amount of food delivered immediately or a larger amount delivered immediately or after delays that increased within sessions. Acutely, morphine decreased responding for the large reinforcer, and the effect was greater when morphine was administered immediately, rather than 6 hr, before sessions. During 8 weeks of daily administration, morphine produced differential effects across pigeons, shifting the delay curve downward in some and upward in others. In all pigeons, tolerance developed to the response rate-decreasing effects of morphine but not to its effects on delay discounting. When chronic morphine treatment was discontinued, rate of responding decreased in 4 pigeons, indicating the emergence of withdrawal; choice of the large reinforcer increased, regardless of delay, in all pigeons, an effect that persisted for weeks. These data suggest that chronic morphine administration has long-lasting effects on choice behavior, which might impact vulnerability to relapse in opioid abusers. PMID:23553726

  4. Cholescintigraphy in acute cholecystitis: use of intravenous morphine

    SciTech Connect

    Choy, D.; Shi, E.C.; McLean, R.G.; Hoschl, R.; Murray, I.P.C.; Ham, J.M.

    1984-04-01

    Conventional cholescintigraphy (60 patients) and a modified protocol (59 patients) were compared in 74 females and 45 males with acute cholecystitis. In the modified protocol, intravenous morphine was administered whenever the gallbladder was not seen 40 minutes after injection of Tc-99m-pyroxylidene-glutamate. Accuracy was 98% with morphine, compared with 88% for the conventional protocol; specificity improved from 83% to 100% with no loss of sensitivity. Low doses of morphine are well tolerated and can result in a highly accurate diagnosis of acute cholecystitis without the need for delayed imaging.

  5. Morphine with adjuvant ketamine versus higher dose of morphine alone for acute pain: a meta-analysis

    PubMed Central

    Ding, Xibing; Jin, Shuqing; Niu, Xiaoyin; Wang, Tingting; Zhao, Xiang; Ren, Hao; Tong, Yao; Li, Quan

    2014-01-01

    Purpose: Ketamine is currently the N-methyl-D-aspartate receptor channel blocker in clinical use. Morphine in pain management is usually limited by adverse effect such as nausea and vomiting. Adjuvant treatment with ketamine may be value in giving better analgesia with fewer adverse effects. The purpose of this meta-analysis was to evaluate the differences when patients received morphine with adjuvant ketamine (MK) compared with higher dose of morphine (MO) for acute pain. Methods: The PubMed, EMBASE and the Cochrane Library databases were searched (Last search performed on July 1, 2014) by two reviewers independently. Data were extracted independently by the same two individuals who searched the studies. Results: A total of 7 trials involving 492 patients were included in the current analysis. We found pain scores were lower in the MK group compared to the MO group [MD 2.19, 95% CI (1.24, 3.13) P<0.00001]. And more patients in the MO required diclofenac [OR 1.97, 95% CI (1.06, 3.67) P=0.03]. Furthermore, morphine plus ketamine can reduced post-operative nausea and vomiting (PONV) [OR 3.71, 95% CI (2.37, 5.80) P<0.00001]. Importantly, the wakefulness scores for the MK group were consistently and significantly better than those for the MO group [MD -1.53, 95% CI (-2.67, -0.40) P=0.008]. Conclusion: The use of ketamine plus 1/4~2/3 the dose of morphine is better than higher dose of morphine alone in reducing pain scores, and rescuing analgesic requirement. It also improved PONV and wakefulness. PMID:25356103

  6. The role of gaseous neurotransmitters in the antinociceptive effects of morphine during acute thermal pain.

    PubMed

    Gou, Gemma; Leánez, Sergi; Pol, Olga

    2014-08-15

    Treatment with a carbon monoxide-releasing molecule (tricarbonyldichlororuthenium(II) dimer, CORM-2) or a classical inducible heme oxygenase (HO-1) inducer (cobalt protoporphyrin IX, CoPP) enhanced the antinociceptive effects of morphine during chronic pain but the role played by these compounds in acute thermal nociception was not evaluated. The effects of CORM-2 and CoPP treatments on the local antinociceptive actions of morphine and their interactions with nitric oxide during acute pain were evaluated by using wild type (WT), neuronal (nNOS-KO) or inducible (iNOS-KO) nitric oxide synthase knockout mice and assessing their thermal nociception to a hot stimulus with the hot plate test. Our results showed that the absence of nNOS or iNOS genes did not alter licking and jumping responses nor the antinociceptive effects produced by morphine indicating that the local thermal inhibitory effects produced by this drug in the absence of inflammation or injury are not mediated by the nitric oxide pathway triggered by nNOS or iNOS enzymes. Moreover, while the systemic administration of CORM-2 or CoPP inhibited licking and jumping latencies in all genotypes, these treatments only enhanced the local inhibition of jumping latencies produced by morphine in WT and nNOS-KO mice which effects were reversed by the peripheral administration of an HO-1 inhibitor. These data indicate that the co-administration of morphine with CORM-2 or CoPP produced remarkable local antinociceptive effects in WT and nNOS-KO mice and reveal that a significant interaction between carbon monoxide and nitric oxide systems occurs on the local antinociceptive effects produced by morphine during acute thermal nociception. PMID:24846012

  7. Increases of CCK mRNA and peptide in different brain areas following acute and chronic administration of morphine.

    PubMed

    Ding, X Z; Bayer, B M

    1993-10-15

    The present study examined whether either acute or chronic administration of morphine resulted in changes in the content of CCK mRNA and CCK immunoactive peptide in selective areas of the rat brain and spinal cord. Two hours after a single injection of morphine (10 mg/kg, s.c.), CCK mRNA significantly increased in the hypothalamus (0.8-fold) and spinal cord (2-fold) relative to the CCK mRNA content in saline-injected controls. No significant differences in CCK mRNA were observed in the frontal cortex, hippocampus, midbrain or brainstem. There were no significant alterations in CCK immunoreactivity in any brain regions and spinal cord after the acute treatment with morphine. Upon repeated morphine administration, the content of CCK mRNA in both the hypothalamus and the spinal cord was further elevated by at least 3-fold. A significant increase of CCK mRNA content in brain stem (2.8-fold) was also observed following chronic morphine administration. In contrast to the acute exposure to morphine, chronic administration resulted in significant increases in CCK immunoactive peptide in hypothalamus (2.6-fold), spinal cord (2.1-fold) and brainstem (1.6-fold), but not in the other brain areas. These results demonstrate that morphine, especially following repeated administrations, stimulates endogenous CCK biosynthesis in selective brain regions. PMID:8242392

  8. Gene expression following acute morphine administration.

    PubMed

    Loguinov, A V; Anderson, L M; Crosby, G J; Yukhananov, R Y

    2001-08-28

    The long-term response to neurotropic drugs depends on drug-induced neuroplasticity and underlying changes in gene expression. However, alterations in neuronal gene expression can be observed even following single injection. To investigate the extent of these changes, gene expression in the medial striatum and lumbar part of the spinal cord was monitored by cDNA microarray following single injection of morphine. Using robust and resistant linear regression (MM-estimator) with simultaneous prediction confidence intervals, we detected differentially expressed genes. By combining the results with cluster analysis, we have found that a single morphine injection alters expression of two major groups of genes, for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins. RNAs for these proteins were mostly downregulated both in the medial striatum and in lumbar part of the spinal cord. These transitory changes were prevented by coadministration of the opioid antagonist naloxone. Data indicate that microarray analysis by itself is useful in describing the effect of well-known substances on the nervous system and provides sufficient information to propose a potentially novel pathway mediating its activity. PMID:11526201

  9. The Effect of Acute and Chronic Morphine on Some Blood Biochemical Parameters in an Inflammatory Condition in Gonadectomized Male Rats

    PubMed Central

    Chahkandi, Mohadeseh; Askari, Nayerreh; Asadikaram, Gholamreza

    2015-01-01

    Background Opiates affect blood factors as well as pain and inflammation in a gender-dependent manner. The aim of the present study was to evaluate the effects of morphine on serum glucose, cholesterol, triglycerides, and urea in gonadectomized and inflammation conditions. Methods Animals were divided as follows: control group, carrageenan and chronic morphine recipients, acute morphine recipients, chronic morphine recipients, carrageenan recipients, acute morphine and carrageenan recipients, gonadectomized group, gonadectomized recipients of carrageenan, gonadectomized recipients of morphine, gonadectomized recipients of chronic morphine, gonadectomized recipients of carrageenan and chronic morphine, gonadectomized recipients of acute morphine and carrageenan. Findings Our results have shown that acute and chronic morphine elevates blood glucose level in the acute and chronic morphine group. Cholesterol level has shown to be increasing in the morphine and carrageenan recipient group compared with a group which merely received morphine. Triglyceride has shown to be decreasing in acute and chronic morphine recipient group compared with control group. A significant increase in serum urea was observed in acute and chronic morphine recipients compared with the carrageenan recipient group. Conclusion Morphine alters the serum glucose, cholesterol, triglyceride, and urea in the normal and inflammatory conditions differently, hence, this finding should be considered in the patients who use morphine as a relief of pain, especially in an inflammatory condition. PMID:26885349

  10. Morphine-augmented cholescintigraphy in the diagnosis of acute cholecystitis

    SciTech Connect

    Kim, E.E.; Pjura, G.; Lowry, P.; Nguyen, M.; Pollack, M.

    1986-12-01

    Cholescintigraphy is a sensitive procedure for diagnosing or excluding acute cholecystitis. However, when rapid diagnosis is critical, the requirement for delayed images (4 hr or more after injection) to minimize the false-positive rate diminishes its utility. We prospectively evaluated 40 cholescintigraphic examinations that did not visualize the gallbladder 1 hr after injection of 99mTc diisopropyliminodiacetic acid. These examinations were then augmented by administration of IV morphine, followed by an additional 30 min of imaging. After the morphine, 18 of these examinations demonstrated visualization of the gallbladder; none subsequently required surgical exploration. Of the remaining 22, who demonstrated persistent nonvisualization of the gallbladder post-morphine, 11 were explored surgically and found to be abnormal. The 11 others were treated medically. Low-dose morphine administered when the gallbladder fails to visualize after 1 hr is a useful adjunct to conventional cholescintigraphy because it reduces the time required to obtain a diagnostic result and decreases the number of false-positive results.

  11. Morphine withdrawal, treatments 1900-30.

    PubMed

    Malcolm, M T

    1999-03-01

    The treatments used between 1900 and 1930 for morphine withdrawal are discussed. The accounts are mainly taken from contemporary textbooks which contain fascinating descriptions of their authors' preferred methods and criticisms of regimes given by other therapists. Delirium, produced by atropine or similar substances, is advocated to cover withdrawal symptoms. The present paper draws parallels with current issues, e.g. withdrawal of opiate under cover of general anaesthesia, follow-up studies and cost-benefit analyses. The particular problems of addicted doctors in 1900-1930 are addressed as are the comparisons then made with non-medically qualified addicts. It is important we keep in mind past mistakes and over-valued ideas so as to reduce any similarly misplaced optimism in our current treatment options. PMID:11623818

  12. Managing acute withdrawal syndrome on patients with heroin and morphine addiction by acupuncture therapy.

    PubMed

    Lu, Po-kuang; Lu, Gabriel P; Lu, Dominic P; Lu, D P; Lu, Winston I

    2004-01-01

    Though there are articles and case reports about using acupuncture to detoxify and to break the narcotic addiction, few articles describe in the West about using acupuncture therapy to treat the emergence of acute withdrawal symptom due to heroin, opium, or morphine. Most often the method of treatment are using the methadone or benzodiazepine and phenoziazine drugs this article describes many years of clinical experience with non-drug approach to treat the acute withdrawal symptoms with acupuncture therapy. Unlike the drug approach, which usually has side effects, there is no adverse effect with acupuncture therapy. PMID:15807100

  13. Morphine treatment alters nucleotidase activities in rat blood serum

    PubMed Central

    Rozisky, Joanna Ripoll; Nonose, Yasmine; Laste, Gabriela; dos Santos, Vinicius Souza; de Macedo, Isabel Cristina; Battastini, Ana Maria Oliveira; Caumo, Wolnei; Torres, Iraci LS

    2012-01-01

    Morphine has been widely used in neonatal pain management. However, this treatment may produce adaptive changes in several physiologic systems. Our laboratory has demonstrated that morphine treatment in neonate rats alters nucleoside triphosphate diphosphohydrolase (NTPDase) activity and gene expression in central nervous system structures. Considering the relationship between the opioid and purinergic systems, our aim was to verify whether treatment with morphine from postnatal days 8 (P8) through 14 (P14) at a dose of 5 µg per day alters NTPDase and 5′-nucleotidase activities in rat serum over the short, medium, and long terms. After the in vivo assay, the morphine group showed increased hydrolysis of all nucleotides at P30, and a decrease in adenosine 5′-diphosphate hydrolysis at P60. Moreover, we found that nucleotidase activities change with age; adenosine 5′-triphosphate hydrolysis activity was lower at P16, and adenosine 5′-monophosphate hydrolysis activity was higher at P60. These changes are very important because these enzymes are the main regulators of blood nucleotide levels and, consequently, nucleotide signaling. Our findings showed that in vivo morphine treatment alters nucleotide hydrolysis in rat blood serum, suggesting that purine homeostasis can be influenced by opioid treatment during the neonatal period.

  14. Pre- and postsynaptic regulation of locus coeruleus neurons after chronic morphine treatment: a study of GIRK knockout mice

    PubMed Central

    Torrecilla, Maria; Quillinan, Nidia; Williams, John T.; Wickman, Kevin

    2008-01-01

    While the acute inhibitory effect of opioids on locus coeruleus (LC) neurons is mediated primarily by the activation of G protein-gated inwardly-rectifying K+ (GIRK) channels, the 3′-5′-cyclic adenosine monophosphate (cAMP)-system has been implicated in the effects of chronic morphine exposure. Presently, the impact of chronic morphine treatment on GIRK-dependent and GIRK-independent mechanisms underlying the opioid-induced inhibition of LC neurons is unclear. Here, opioid-induced postsynaptic inhibition was studied in LC neurons from wild-type and GIRK2/GIRK3-/- mice at baseline and following chronic morphine treatment. The postsynaptic inhibition of LC neurons caused by the opioid agonist [Met]5 enkephalin (ME) was unaffected by chronic morphine treatment in mice of both genotypes. Furthermore, chronic morphine treatment had no effect on the forskolin augmentation of the ME-induced current in wild-type LC neurons, and only a minor effect on the ME-induced current in LC neurons from GIRK2/GIRK3-/- mice. Chronic morphine treatment did, however, lead to an increased frequency of spontaneous excitatory postsynaptic currents (EPSCs) in the LC. Interestingly, while forskolin augmented the EPSC frequency similarly in untreated and morphine-treated wild-type mice, as well as untreated GIRK2/GIRK3-/- mice, it failed to increase the frequency of EPSCs in morphine-treated GIRK2/GIRK3-/- mice. Altogether, the findings suggest that chronic morphine treatment exerts little impact on ion channels and signaling pathways that mediate the postsynaptic inhibitory effects of opioids, but does enhance excitatory neurotransmission in the mouse LC. PMID:18702733

  15. Efficacy of Intravenous Paracetamol Versus Intravenous Morphine in Acute Limb Trauma

    PubMed Central

    Jalili, Mohammad; Mozaffarpour Noori, Ali; Sedaghat, Mojtaba; Safaie, Arash

    2016-01-01

    Background: Efficient pain management is one of the most important components of care in the field of emergency medicine. Objectives: This study was conducted to compare intravenous paracetamol and intravenous morphine sulfate for acute pain reduction in patients with limb trauma. Patients and Methods: In a randomized double-blinded clinical trial, all patients (aged 18 years and older) with acute limb trauma and a pain score of greater than 3/10 in the emergency department were recruited; they received either 1 g intravenous paracetamol or 0.1 mg/kg intravenous morphine sulfate over 15 minutes. The primary outcome was the pain score measured on a numerical rating scale at 0, 15 and 30 minutes after commencing drug administration. The requirement for rescue analgesia and the frequency of adverse reactions were also recorded. Results: Sixty patients randomly received either IV paracetamol (n = 30) or IV morphine (n = 30). The mean reduction in numerical rating scale pain intensity scores at 30 minutes was 3.86 (± 1.61) for paracetamol, and 2.16 (± 1.39) for morphine. However, pain relief was significantly higher in the paracetamol group compared to the morphine group (P < 0.001). Four patients in the paracetamol group and 15 patients in the morphine group needed rescue analgesia and the difference was significant (P = 0.05). Conclusions: Intravenous paracetamol appears to provide better analgesia than intravenous morphine in acute limb trauma. Further larger studies are required. PMID:27218042

  16. RSK2 Signaling in Medial Habenula Contributes to Acute Morphine Analgesia

    PubMed Central

    Darcq, Emmanuel; Befort, Katia; Koebel, Pascale; Pannetier, Solange; Mahoney, Megan K; Gaveriaux-Ruff, Claire; Hanauer, André; Kieffer, Brigitte L

    2012-01-01

    It has been established that mu opioid receptors activate the ERK1/2 signaling cascade both in vitro and in vivo. The Ser/Thr kinase RSK2 is a direct downstream effector of ERK1/2 and has a role in cellular signaling, cell survival growth, and differentiation; however, its role in biological processes in vivo is less well known. Here we determined whether RSK2 contributes to mu-mediated signaling in vivo. Knockout mice for the rsk2 gene were tested for main morphine effects, including analgesia, tolerance to analgesia, locomotor activation, and sensitization to this effect, as well as morphine withdrawal. The deletion of RSK2 reduced acute morphine analgesia in the tail immersion test, indicating a role for this kinase in mu receptor-mediated nociceptive processing. All other morphine effects and adaptations to chronic morphine were unchanged. Because the mu opioid receptor and RSK2 both show high density in the habenula, we specifically downregulated RSK2 in this brain metastructure using an adeno-associated-virally mediated shRNA approach. Remarkably, morphine analgesia was significantly reduced, as observed in the total knockout animals. Together, these data indicate that RSK2 has a role in nociception, and strongly suggest that a mu opioid receptor–RSK2 signaling mechanism contributes to morphine analgesia at the level of habenula. This study opens novel perspectives for both our understanding of opioid analgesia, and the identification of signaling pathways operating in the habenular complex. PMID:22218090

  17. [Acute respiratory distress subordinate to a morphine overdose during a frail elderly patient controlled analgesia].

    PubMed

    Ades, A; Compère, V; Abriou, C; Baert, O; Fourdrinier, V; Dureuil, B

    2009-04-01

    We describe a case-report of an 85-year-male patient with a patient-controlled analgesia (PCA) after a total hip arthroplasty. Four hours after surgery, acute respiratory distress secondary to a morphine overdose occurred, requiring an antagonisation with naloxone. Morphine overdose during a PCA was always caused by a wrong use of the pump. In this case-report, no mistake of programming or administration's use was found. Too important morphine's doses managed in comparison with the patient's age and his renal failure could explain this morphine's accumulation and the respiratory distress. This observation reminds us the obligation to determine the optimal posology in accordance with the rate of glomerular filtration estimated by Cockcroft and Gault formula for patients using a PCA. PMID:19361945

  18. Involvement of neuropeptide Y in the acute, chronic and withdrawal responses of morphine in nociception in neuropathic rats: behavioral and neuroanatomical correlates.

    PubMed

    Upadhya, Manoj A; Dandekar, Manoj P; Kokare, Dadasaheb M; Singru, Praful S; Subhedar, Nishikant K

    2009-08-01

    Although morphine is a potent antinociceptive agent, its chronic use developed tolerance in neuropathic pain (NP). Furthermore, opioid antagonist naloxone attenuated the antinociceptive effect of neuropeptide Y (NPY). The present study investigated the role of NPY and NPY Y1/Y5 receptors in acute and chronic actions of morphine in neuropathic rats using thermal paw withdrawal test and immunocytochemistry. In acute study, intracerebroventricular (icv) administration of morphine, NPY or NPY Y1/Y5 receptors agonist [Leu(31),Pro(34)]-NPY produced antinociception, whereas selective NPY Y1 receptors antagonist BIBP3226 caused hyperalgesia. While NPY or [Leu(31),Pro(34)]-NPY potentiated, BIBP3226 attenuated morphine induced antinociception. Chronic icv infusion of morphine via osmotic minipumps developed tolerance to its antinociceptive effect, and produced hyperalgesia following withdrawal. However, co-administration of NPY or [Leu(31),Pro(34)]-NPY prevented the development of tolerance and withdrawal hyperalgesia. Sciatic nerve ligation resulted in significant increase in the NPY-immunoreactive (NPY-ir) fibers in ventrolateral periaqueductal gray (VLPAG) and locus coeruleus (LC); fibers in the dorsal part of dorsal raphe nucleus (DRD) did not respond. While chronic morphine treatment significantly reduced NPY-ir fibers in VLPAG and DRD, morphine withdrawal triggered significant augmentation in NPY-immunoreactivity in the VLPAG. NPY-immunoreactivity profile of LC remained unchanged in all the morphine treatment conditions. Furthermore, removal of sciatic nerve ligation reversed the effects of NP, increased pain threshold and restored NPY-ir fiber population in VLPAG. NPY, perhaps acting via Y1/Y5 receptors, might profoundly influence the processing of NP information and interact with the endogenous opioid system primarily within the framework of the VLPAG. PMID:19556004

  19. The on- and off-target effects of morphine in acute coronary syndrome: A narrative review.

    PubMed

    McCarthy, Cian P; Mullins, Kieran V; Sidhu, Sunjeet S; Schulman, Steven P; McEvoy, John W

    2016-06-01

    With potent analgesic properties, perceived hemodynamic benefits and limited alternatives, morphine is the analgesic mainstay for patients with nitrate resistant chest pain due to acute Myocardial Infarction (MI). However, observational data suggest that morphine administration during MI may have negative consequences. While vomiting, hypotension and respiratory depression are established side effects, recent reports have demonstrated attenuated and delayed oral anti-platelet agent absorption, as well as suboptimal reperfusion after MI, all of which may translate into adverse cardiovascular outcomes. These data have resulted in reduced support for morphine in recent European and U.S. clinical practice guidelines for MI; despite the absence of any prospective randomized outcomes trials addressing this question. As such, randomized trials are now necessary to confirm whether or not morphine, which is administered in up to 30% of MI cases, causes adverse clinical outcomes in these patients. However, given that placebo-controlled randomized trial designs evaluating morphine in MI are limited by an ethical requirement for appropriate analgesia, alternative investigational approaches may be necessary. In this article we review the updated evidence for morphine in MI and outline novel strategies that may facilitate future investigation of this clinical dilemma. PMID:27264228

  20. Comparison of Clinical Efficacy of Intravenous Acetaminophen with Intravenous Morphine in Acute Renal Colic: A Randomized, Double-Blind, Controlled Trial

    PubMed Central

    Forouzan, Arash; Asgari Darian, Ali; Feli, Maryam; Barzegari, Hassan; Khavanin, Ali

    2014-01-01

    The aim of this study was to compare the clinical efficacy of intravenous acetaminophen with intravenous morphine in acute renal colic pain management. In this double-blind controlled trial, patients aged 18–55 years, diagnosed with acute renal colic, who met the inclusion and exclusion criteria, were randomized into two groups. First, using the visual analogue scale (VAS), intensity of pain was assessed in both groups. Then, one gram of intravenous acetaminophen or 0.1 mg/kg morphine was infused in 100 mL normal saline to either acetaminophen or morphine group. Intensity of pain was reassessed in 15, 30, 45, and 60 minutes according to VAS criteria. Finally, data from 108 patients were analyzed, 54 patients in each group. No significant difference was observed between the two groups in regard to sex (P = 0.13), mean age (P = 0.54), and baseline visual analogue score (P = 0.21). A repeated measure analysis of variance revealed that the difference between the two treatments was significant (P = 0.0001). The VAS reduction at primary endpoint (30 min after drug administration) was significantly higher in the acetaminophen group than in the morphine group (P = 0.0001). This study demonstrated that intravenous acetaminophen could be more effective than intravenous morphine in acute renal colic patients' pain relief. PMID:25197573

  1. Meperidine (pethidine) versus morphine in acute pain management of opioid-dependent patients

    PubMed Central

    Solhi, Hassan; Sanaei-Zadeh, Hossein; Solhi, Sadra; Azizi Nadian, Mohammad Ali; Gharibi, Morteza; Sadeghi Sedeh, Bahman

    2016-01-01

    The present study aimed to evaluate the effectiveness of morphine and meperidine (pethidine) as pain relief in opioid-dependent patients with acute pain. A total of 122 opioid-dependent patients with acute pain were included in the study. Their pain severity was assessed, using visual analog scale (VAS) scores ranging from 0 to 10. The patients randomly received intravenous morphine (up to 0.15 mg/kg) or meperidine (up to 1.5 mg/kg) for pain control by patient control analgesia (PCA) pump. The clinical opioid withdrawal scale (COWS) was employed for the assessment of withdrawal symptoms. The pain relief and the emergence of withdrawal symptoms were measured at 15, 30, and 60 minutes after drug administration. The patients who received morphine reported a better pain control compared to those who received meperidine (mean ± standard deviation [SD] VAS scores 4.11±1.90 vs 5.85±2.08 at the end of the study; P<0.001). On the other hand, the patients who received meperidine indicated prominent withdrawal symptoms (mean ± SD COWS scores 4.80±2.18 vs. 1.98±0.82 at the end of the study; P<0.001). Our findings revealed that morphine can be recommended in acute pain management of opioid-dependent patients. In addition, emergency physicians should ask their patients about any drug dependence before selecting the appropriate drug for their acute pain management.

  2. Meperidine (pethidine) versus morphine in acute pain management of opioid-dependent patients.

    PubMed

    Solhi, Hassan; Sanaei-Zadeh, Hossein; Solhi, Sadra; Azizi Nadian, Mohammad Ali; Gharibi, Morteza; Sadeghi Sedeh, Bahman

    2016-01-01

    The present study aimed to evaluate the effectiveness of morphine and meperidine (pethidine) as pain relief in opioid-dependent patients with acute pain. A total of 122 opioid-dependent patients with acute pain were included in the study. Their pain severity was assessed, using visual analog scale (VAS) scores ranging from 0 to 10. The patients randomly received intravenous morphine (up to 0.15 mg/kg) or meperidine (up to 1.5 mg/kg) for pain control by patient control analgesia (PCA) pump. The clinical opioid withdrawal scale (COWS) was employed for the assessment of withdrawal symptoms. The pain relief and the emergence of withdrawal symptoms were measured at 15, 30, and 60 minutes after drug administration. The patients who received morphine reported a better pain control compared to those who received meperidine (mean ± standard deviation [SD] VAS scores 4.11±1.90 vs 5.85±2.08 at the end of the study; P<0.001). On the other hand, the patients who received meperidine indicated prominent withdrawal symptoms (mean ± SD COWS scores 4.80±2.18 vs. 1.98±0.82 at the end of the study; P<0.001). Our findings revealed that morphine can be recommended in acute pain management of opioid-dependent patients. In addition, emergency physicians should ask their patients about any drug dependence before selecting the appropriate drug for their acute pain management. PMID:27621675

  3. Pre-conditioned place preference treatment of chloral hydrate interrupts the rewarding effect of morphine.

    PubMed

    Sun, YongMei; Zong, Wei; Zhou, MuRu; Ma, YuanYe; Wang, JianHong

    2015-08-01

    The medical use of morphine as a pain killer is hindered by its side effects including dependence and further addiction. As the prototypical μ receptor agonist, morphine's rewarding effect can be measured by conditioned place preference (CPP) paradigms in animals. Chloral hydrate is a clinical sedative. Using a morphine CPP paradigm that mainly contains somatosensory cues, we found that pre-CPP treatment in rats using chloral hydrate for 6 consecutive days could disrupt the establishment of CPP in a U shape. Chloral hydrate had no effect on the body weight of rats. Our results indicate that prior treatment with chloral hydrate can interrupt the rewarding effect of morphine. PMID:26013578

  4. PolyMorphine: an innovative biodegradable polymer drug for extended pain relief

    PubMed Central

    Rosario-Meléndez, Roselin; Harris, Carolyn L.; Delgado-Rivera, Roberto; Yu, Lei; Uhrich, Kathryn E.

    2012-01-01

    Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed “PolyMorphine”, was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, and infrared spectroscopy. The weight-average molecular weight and the thermal properties were determined. The hydrolytic degradation pathway of the polymer was determined by in vitro studies, showing that free morphine is released. In vitro cytocompatibility studies demonstrated that PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice showed that PolyMorphine provides analgesia for 3 days, 20 times the analgesic window of free morphine. The animals retained full responsiveness to morphine after being subjected to an acute morphine challenge. PMID:22877734

  5. The effects of morphine treatment on the NCAM and its signaling in the MLDS of rats.

    PubMed

    Cao, Jun Ping; Wang, Hong Jun; Li, Li; Zhang, Su Ming

    2016-10-01

    Prolonged exposure to opiates induces a constellation of neuroadaptations, especially in the mesolimbic dopamine system (MLDS), which leads to alteration in the function of motivational circuitry. The neural cell adhesion molecule (NCAM) mediates cell-cell interactions and plays an important role in processes associated with neural plasticity. Moreover, it has been shown that NCAM were related to risk of alcoholism in human populations. Here, coimmunoprecipitation and western blotting were used to investigate whether morphine treatment induced alteration of the expression of NCAM or its signaling level in MLDS. The rats receiving escalating dose of morphine treatment were divided into three groups: morphine 1d, 3d and 5d group, which were injected subcutaneously with morphine hydrochloride for 1 day, 3 days and 5 days, respectively. Twelve hours after the last injection, animals were sacrificed and the tissues of ventral tegmental area (VTA), prefrontal cortex (PFC) and nucleus accumbens (NAc) were punched out to examine the expression of NCAM or its signaling level. The results showed that morphine treatment had no significant effect on the expression of NCAM, but downregulated the phosphorylation of NCAM-associated focal adhesion kinase (FAK) in the VTA and PFC of rats. In the NAc of rats, however, the expression of NCAM and its signaling were not altered significantly by morphine treatment. These results indicated that the downregulation of NCAM signaling in the VTA and PFC might be involved in the formation of morphine addiction. PMID:26821693

  6. The Comparison of Apotel plus Low Dose of Morphine and Full Dose of Morphine in Pain Relief in Patients with Acute Renal Colic

    PubMed Central

    Morteza-Bagi, Hamid Reza; Amjadi, Mohsen; Mirzaii-Sousefidi, Reyhaneh

    2015-01-01

    Background Renal colic is an acute flank pain which may radiate to the groin, lower abdomen, or external genitalia due to the passage of a urinary stones. Pain management is the most important task in emergency wards when a patient with renal colic attends. This study aims to compare intravenous acetaminophen plus a low dose of morphine with a full dose of morphine in renal colic. Methods In present randomized clinical trial, 100 patients with confirmed renal colic were recruited from the Emergency Ward of Imam Reza Teaching Hospital affiliated to Tabriz University of Medical Sciences, Iran, during a one-year period. These patients randomly received either intravenous acetaminophen (Apotel, 1 g) plus a low dose of morphine (n = 50), or a high dose of morphine (5 mg) (n = 50). Visual analogue scale (VAS) was used for reporting pain during 35 minutes. Side effects and rescue analgesic demand were recorded after 30 minutes. Findings The two groups were matched for the patients' age and gender. Intra-group analysis showed significant gradual decreases in pain intensity after 35 minutes for both groups. Inter-group analysis, however, did not show a significant difference between the two groups in this regard. There was no significant difference between the two groups in terms of side effects. The rate of rescue analgesic demand was 36% in the first and 40% in the second group (P = 0.68). Conclusion According to the results study, Apotel plus a low dose of morphine is at least as effective and safe as a full dose of morphine in patients with renal colic. PMID:26322213

  7. Atrial Fibrillation is Associated With Morphine Treatment in Female Breast Cancer Patients

    PubMed Central

    Lee, Cynthia Wei-Sheng; Muo, Chih-Hsin; Liang, Ji-An; Lin, Ming-Chia; Kao, Chia-Hung

    2016-01-01

    Abstract We investigated the relationship between morphine treatment and the risk of atrial fibrillation (AF) in female patients with breast cancer. We identified a malignancy cohort of 73,917 female breast cancer patients without an AF history before the date of breast cancer diagnosis between 2000 and 2010 by using the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. This malignancy cohort was divided into morphine and comparison cohorts comprising 18,671 and 55,246 patients, respectively, and the incidences of newly diagnosed AF were calculated. We used the Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of AF. The effect of morphine was assessed through multivariable Cox proportional hazard regression controlling for age, the Charlson comorbidity index (CCI) score, and the use of bisphosphonates and paclitaxel. Compared with nonmorphine users, patients who received morphine exhibited a 4.37-fold (95% CI = 3.56–5.36) increase in the risk of developing AF. The risk of AF increased as the CCI score increased, but decreased in patients with tamoxifen treatment. This risk is especially significant in current morphine users of all ages and with low CCI score. AF risk increased as the duration of morphine use lengthened (P for trend <0.0001). The incidence of AF in female breast cancer patients in Taiwan is associated with morphine, but prevented by tamoxifen treatment. PMID:26986153

  8. Global Changes in the Rat Heart Proteome Induced by Prolonged Morphine Treatment and Withdrawal

    PubMed Central

    Drastichova, Zdenka; Skrabalova, Jitka; Jedelsky, Petr; Neckar, Jan; Kolar, Frantisek; Novotny, Jiri

    2012-01-01

    Morphine belongs among the most commonly used opioids in medical practice due to its strong analgesic effects. However, sustained administration of morphine leads to the development of tolerance and dependence and may cause long-lasting alterations in nervous tissue. Although proteomic approaches enabled to reveal changes in multiple gene expression in the brain as a consequence of morphine treatment, there is lack of information about the effect of this drug on heart tissue. Here we studied the effect of 10-day morphine exposure and subsequent drug withdrawal (3 or 6 days) on the rat heart proteome. Using the iTRAQ technique, we identified 541 proteins in the cytosol, 595 proteins in the plasma membrane-enriched fraction and 538 proteins in the mitochondria-enriched fraction derived from the left ventricles. Altogether, the expression levels of 237 proteins were altered by morphine treatment or withdrawal. The majority of changes (58 proteins) occurred in the cytosol after a 3-day abstinence period. Significant alterations were found in the expression of heat shock proteins (HSP27, α-B crystallin, HSP70, HSP10 and HSP60), whose levels were markedly up-regulated after morphine treatment or withdrawal. Besides that morphine exposure up-regulated MAPK p38 (isoform CRA_b) which is a well-known up-stream mediator of phosphorylation and activation of HSP27 and α-B crystallin. Whereas there were no alterations in the levels of proteins involved in oxidative stress, several changes were determined in the levels of pro- and anti-apoptotic proteins. These data provide a complex view on quantitative changes in the cardiac proteome induced by morphine treatment or withdrawal and demonstrate great sensitivity of this organ to morphine. PMID:23056601

  9. Morphine effects on gentamicin disposition and toxicity in mice.

    PubMed

    Hurwitz, A; Garty, M; Ben-Zvi, Z

    1988-05-01

    Morphine has been shown to reduce renal and hepatic clearance of several xenobiotics in rodents. After iv administration of gentamicin, 10 to 30 mg/kg, its plasma levels were elevated in mice given morphine, 20 mg/kg sc. Plasma clearance of gentamicin was nearly halved by morphine, due primarily to lowering of the elimination constant of gentamicin from 0.03 to 0.02 min-1 (p less than 0.01). Morphine also significantly reduced urine levels of gentamicin and urine volume. In mice given naloxone, 2 mg/kg sc, morphine did not significantly raise plasma levels of gentamicin nor reduce its elimination into urine. Mice were made tolerant by morphine administration for 9 days at ascending doses to 100 mg/kg twice daily. An acute challenge with morphine, 20 mg/kg, was less effective in raising plasma levels of gentamicin or lowering its urinary elimination in tolerant mice than after chronic saline treatment. Partial tolerance to acutely administered morphine and reversal of morphine effects by naloxone suggest opioid receptor-mediated reduction of glomerular filtration by morphine in mice. Despite marked elevation of plasma gentamicin levels in morphine-treated mice, narcotic administration did not significantly increase the acute toxicity of a single dose of gentamicin. LD50 of acutely administered iv gentamicin was 51.6 mg/kg after saline and 45.3 mg/kg after treatment with morphine, 20 mg/kg sc. However, this dose of morphine enhanced the lethality of intravenously infused gentamicin. Morphine administration significantly reduced the dose of infused gentamicin needed to achieve the critical lethal plasma level. PMID:3368920

  10. Haemodynamic effects of intravenous morphine in patients with acute myocardial infarction complicated by severe left ventricular failure.

    PubMed Central

    Timmis, A D; Rothman, M T; Henderson, M A; Geal, P W; Chamberlain, D A

    1980-01-01

    The haemodynamic effects of intravenous morphine sulphate (0.2 mg/kg body weight) were measured in 10 patients with acute myocardial infarction complicated by severe left ventricular failure. Fifteen minutes after morphine injection there was a significant fall in mean heart rate (from 109 to 101 beats/min) and mean systemic arterial pressure (from 80 to 65 mm HG), and a small fall in mean cardiac index (from 2.4 to 2.21/min/m2). Haemodynamic changes at 45 minutes were similar. Neither stroke index nor indirect left ventricular filling pressure (measured as pulmonary artery end-diastolic pressure) were consistently improved 15 or 45 minutes after injection. The useful action of morphine in relieving distressing cardiac dyspnoea is not adequately explained by systemic venous blood pooling. These results suggest that the effects of morphine on the central nervous system are more important. Images p982-a PMID:7417767

  11. Evaluation of NK and LAK cell activities in neoplastic patients during treatment with morphine.

    PubMed

    Provinciali, M; Di Stefano, G; Raffaeli, W; Pari, G; Desiderio, F; Fabris, N

    1991-07-01

    The cytotoxic activity of Natural Killer (NK) and Lymphokine Activated Killer (LAK) cells in neoplastic patients with or without antalgic treatment was studied. NK cell activity was found reduced in untreated neoplastic patients when compared to healthy subjects. The atalgic treatment with morphine (orally or intrathecally administered) was able to significantly reduce the mean values of NK cell activity found in cancer patients. In three patients the cytotoxicity of NK cells significantly decreased during transfer from oral to intrathecal administration of morphine. In contrast to the NK cell function, the development of LAK cell activity significantly increased in neoplastic patients when compared to healthy controls. Further increments were obtained during treatment with morphine. The oral treatment with morphine was able to determine a higher induction of LAK cells than the intrathecal administration of the drug. Besides providing new knowledge on the effect of morphine on immune system our findings suggest that, in order to include neoplastic patients in clinical trials of adoptive immunotherapy with LAK cells and interleukin-2 (IL-2), the antalgic therapy with oral administration of morphine may represent a better solution than the intrathecal administration of the drug. PMID:1774133

  12. Combined Treatment with Morphine and Δ9-Tetrahydrocannabinol in Rhesus Monkeys: Antinociceptive Tolerance and Withdrawal.

    PubMed

    Gerak, L R; France, C P

    2016-05-01

    Opioid receptor agonists are effective for treating pain; however, tolerance and dependence can develop with repeated use. Combining opioids with cannabinoids can enhance their analgesic potency, although it is less clear whether combined treatment alters opioid tolerance and dependence. In this study, four monkeys received 3.2 mg/kg morphine alone or in combination with 1 mg/kg Δ(9)-tetrahydrocannabinol (THC) twice daily; the antinociceptive effects (warm water tail withdrawal) of morphine, the cannabinoid receptor agonists WIN 55,212 [(R)-(1)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] and CP 55,940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), and the κ opioid receptor agonist U-50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide methanesulfonate) were examined before, during, and after treatment. To determine whether concurrent THC treatment altered morphine dependence, behavioral signs indicative of withdrawal were monitored when treatment was discontinued. Before treatment, each drug increased tail withdrawal latency to 20 seconds (maximum possible effect). During treatment, latencies did not reach 20 seconds for morphine or the cannabinoids up to doses 3- to 10-fold larger than those that were fully effective before treatment. Rightward and downward shifts in antinociceptive dose-effect curves were greater for monkeys receiving the morphine/THC combination than monkeys receiving morphine alone. When treatment was discontinued, heart rate and directly observable withdrawal signs increased, although they were generally similar in monkeys that received morphine alone or with THC. These results demonstrated that antinociceptive tolerance was greater during treatment with the combination, and although treatment conditions were sufficient to result in the development of dependence on morphine, withdrawal was not

  13. The efficacy of intrathecal morphine and clonidine in the treatment of pain after spinal cord injury.

    PubMed

    Siddall, P J; Molloy, A R; Walker, S; Mather, L E; Rutkowski, S B; Cousins, M J

    2000-12-01

    We performed a double-blinded, randomized, controlled trial in 15 patients to determine the efficacy of intrathecal morphine or clonidine, alone or combined, in the treatment of neuropathic pain after spinal cord injury. The combination of morphine and clonidine produced significantly more pain relief than placebo 4 h after administration; either morphine or clonidine alone did not produce as much pain relief. In addition, lumbar and cervical cerebrospinal fluid (CSF) concentrations, sampled at these levels at different times after administration were examined for a relationship between pain relief and CSF drug concentration. Lumbar CSF drug concentrations were initially several orders of magnitude larger than those in cervical CSF. After 1-2 h, the concentrations of morphine in cervical CSF markedly exceeded those of clonidine. The concentration of morphine in the cervical CSF and the degree of pain relief correlated significantly. We conclude that intrathecal administration of a mixture of clonidine and morphine is more effective than either drug administered alone and is related to the CSF-borne drug concentration above the level of spinal cord injury. If there is pathology that may restrict CSF flow, consideration should be given to intrathecal administration above the level of spinal cord damage to provide an adequate drug concentration in this region. PMID:11094007

  14. Intrathecal morphine attenuates acute opioid tolerance secondary to remifentanil infusions during spinal surgery in adolescents

    PubMed Central

    Tripi, Paul A; Kuestner, Matthew E; Poe-Kochert, Connie S; Rubin, Kasia; Son-Hing, Jochen P; Thompson, George H; Tobias, Joseph D

    2015-01-01

    Introduction The unique pharmacokinetic properties of remifentanil with a context-sensitive half-life unaffected by length of infusion contribute to its frequent use during anesthetic management during posterior spinal fusion in children and adolescents. However, its intraoperative administration can lead to increased postoperative analgesic requirements, which is postulated to be the result of acute opioid tolerance with enhancement of spinal N-methyl-D-aspartate receptor function. Although strategies to prevent or reduce tolerance have included the coadministration of longer acting opioids or ketamine, the majority of these studies have demonstrated little to no benefit. The current study retrospectively evaluates the efficacy of intrathecal morphine (ITM) in preventing hyperalgesia following a remifentanil infusion. Methods We retrospectively analyzed 54 patients undergoing posterior spinal fusion with segmental spinal instrumentation, to evaluate the effects of ITM on hyperalgesia from remifentanil. Patients were divided into two groups based on whether they did or did not receive remifentanil during the surgery: no remifentanil (control group) (n=27) and remifentanil (study group) (n=27). Data included demographics, remifentanil dose and duration, Wong–Baker visual analog scale postoperative pain scores, and postoperative intravenous morphine consumption in the first 48 postoperative hours. Results The demographics of the two study groups were similar. There were no differences in the Wong–Baker visual analog scale pain scores in the postanesthesia care unit and on postoperative days 1 and 3. Pain scores were higher in the remifentanil group on postoperative day 2 (2.9 vs 3.8). Postoperative morphine requirements were similar between the two groups (0.029 vs 0.017 mg/kg/48 h for the control group and the study group, respectively). Conclusion In patients receiving preincisional ITM during spinal surgery, intraoperative remifentanil does not increase

  15. CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats

    PubMed Central

    Wills, Kiri L.; Vemuri, Kiran; Kalmar, Alana; Lee, Alan; Limebeer, Cheryl L.; Makriyannis, Alexandros

    2014-01-01

    Rationale Modulation of the endocannabinoid system has been found to interfere with opiate withdrawal. The potential of activation and blockade of the endocannabinoid system to prevent the aversive-affective state of naloxone-precipitated morphine withdrawal (MWD) was investigated in a one-trial conditioned place aversion (CPA) paradigm. Objective CPA provides a sensitive measure of the motivational effects of acute MWD. The potential of the fatty acid amide hydrolase (FAAH) inhibitors, URB597 and PF-3845, the CB1 antagonist/inverse agonist, AM251, and the neutral CB1 antagonists, AM4113 and AM6527 (oral), to interfere with establishment of a MWD-induced CPA was investigated. As well, the potential of AM251 and AM4113 to interfere with reinstatement of a previously established MWD-induced CPA was investigated. Materials and methods Using a one-trial place conditioning paradigm, rats were administered naloxone (1 mg/kg, subcutaneous (sc)) 24 h after receiving a high dose of morphine (20 mg/kg, sc) and were placed on the conditioning floor. To determine the effect of each pretreatment drug on the establishment of the MWD-induced CPA, URB597 (0.3 mg/kg, intraperitoneally (ip)), PF-3845 (10 mg/kg, ip), AM251 (1 or 2.5 mg/kg, ip), AM4113 (1 or 2.5 mg/kg, ip), and AM6527 (5 mg/kg, oral) were administered prior to conditioning. Results AM251 (2.5, but not 1 mg/k), AM4113, and AM6527, but not URB597 or PF-3845, interfered with the establishment of the MWD-induced CPA. AM251 and AM4113 did not prevent reinstatement of the CPA. Conclusions Neutral antagonism of the CB1 receptor reduces the aversive affective properties of morphine withdrawal. PMID:24770676

  16. Differential desensitization of mu- and delta- opioid receptors in selected neural pathways following chronic morphine treatment.

    PubMed Central

    Noble, F.; Cox, B. M.

    1996-01-01

    1. Morphine produces a plethora of pharmacological effects and its chronic administration induces several side-effects. The cellular mechanisms by which opiates induce these side-effects are not fully understood. Several studies suggest that regulation of adenylyl cyclase activity by opioids and other transmitters plays an important role in the control of neural function. 2. The aim of this study was to evaluate desensitization of mu- and delta- opioid receptors, defined as a reduced ability of opioid agonists to inhibit adenylyl cyclase activity, in four different brain structures known to be involved in opiate drug actions: caudate putamen, nucleus accumbens, thalamus and periaqueductal gray (PAG). Opiate regulation of adenylyl cyclase in these regions has been studied in control and morphine-dependent rats. 3. The chronic morphine treatment used in the present study (subcutaneous administration of 15.4 mg morphine/rat/day for 6 days via osmotic pump) induced significant physical dependence as indicated by naloxone-precipitated withdrawal symptoms. 4. Basal adenylyl cyclase in the four brain regions was not modified by this chronic morphine treatment. In the PAG and the thalamus, a desensitization of mu- and delta-opioid receptors was observed, characterized by a reduced ability of Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAMGO; mu), Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE; delta) and [D-Ala2]-deltorphin-II (DT-II; delta) to inhibit adenylyl cyclase, activity following chronic morphine treatment. 5. The opioid receptor desensitization in PAG and thalamus appeared to be heterologous since the metabotropic glutamate receptor agonists, L-AP4 and glutamate, and the 5-hydroxytryptamine (5-HT)1A receptor agonist, R(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), also showed reduced inhibition of adenylyl cyclase activity following chronic morphine treatment. 6. In the nucleus accumbens and the caudate putamen, desensitization of delta-opioid receptor

  17. Effect of morphine on synaptosomal Ca++ uptake.

    PubMed

    Guerrero-Munoz, F; Cerreta, K V; Guerrero, M L; Way, E L

    1979-04-01

    The effect of morphine on the uptake of 45Ca++ was studied in synaptosomes from mouse brain using two procedures, centrifugation and filtration. The addition of morphine (1.7 x 10(-7) or 3.4 x 10(-7) M) reduced 45CA++ uptake by either technique, although the basal 45Ca++ uptake by the filtration method was approximately 7-fold higher than that by the centrifugation procedure. Similar effects were obtained after acute morphine treatment with 10 mg/kg s.c. Previous naloxone in vitro treatment (1.9 x 10(-8) M) or in vivo administration (2 mg/kg s.c.) reversed the morphine inhibition of the 45Ca++ uptake. On the other hand, after the animal was rendered tolerant and dependent by morphine pellet implantation, an enhancement of the synaptosomal 45Ca++ uptake was observed. It is concluded that changes in Ca++ fluxes in synaptosomes observed after acute and chronic morphine treatment may be involved with morphine pharmacological action related with analgesia, tolerance and physical dependence. PMID:571016

  18. Comparison of (+)- and (-)-Naloxone on the Acute Psychomotor-Stimulating Effects of Heroin, 6-Acetylmorphine, and Morphine in Mice.

    PubMed

    Eriksen, Guro Søe; Andersen, Jannike Mørch; Boix, Fernando; Bergh, Marianne Skov-Skov; Vindenes, Vigdis; Rice, Kenner C; Huestis, Marilyn A; Mørland, Jørg

    2016-08-01

    Toll-like receptor 4 (TLR4) signaling is implied in opioid reinforcement, reward, and withdrawal. Here, we explored whether TLR4 signaling is involved in the acute psychomotor-stimulating effects of heroin, 6-acetylmorphine (6-AM), and morphine as well as whether there are differences between the three opioids regarding TLR4 signaling. To address this, we examined how pretreatment with (+)-naloxone, a TLR4 active but opioid receptor (OR) inactive antagonist, affected the acute increase in locomotor activity induced by heroin, 6-AM, or morphine in mice. We also assessed the effect of pretreatment with (-)-naloxone, a TLR4 and OR active antagonist, as well as the pharmacokinetic profiles of (+) and (-)-naloxone in the blood and brain. We found that (-)-naloxone reduced acute opioid-induced locomotor activity in a dose-dependent manner. By contrast, (+)-naloxone, administered in doses assumed to antagonize TLR4 but not ORs, did not affect acute locomotor activity induced by heroin, 6-AM, or morphine. Both naloxone isomers exhibited similar concentration versus time profiles in the blood and brain, but the brain concentrations of (-)-naloxone reached higher levels than those of (+)-naloxone. However, the discrepancies in their pharmacokinetic properties did not explain the marked difference between the two isomers' ability to affect opioid-induced locomotor activity. Our results underpin the importance of OR activation and do not indicate an apparent role of TLR4 signaling in acute opioid-induced psychomotor stimulation in mice. Furthermore, there were no marked differences between heroin, 6-AM, and morphine regarding involvement of OR or TLR4 signaling. PMID:27278234

  19. Effect of cinitapride in isolated ileum obtained from guinea-pigs treated with morphine.

    PubMed

    Colado, M I; Alfaro, M J; del Val, V L; Martín, M I

    1991-01-01

    1. Cinitapride enhanced the contractile response induced by electrical stimulation in the guinea-pig myenteric plexus-longitudinal muscle strip preparations. 2. The contractile force was significantly increased in strips pretreated with morphine "in vitro" and in tolerant strips. 3. However when tissues were obtained from tolerant guinea-pigs and morphine was not added to the organ bath (morphine-abstinence), the cinitapride effect was significantly decreased. 4. Although further work is required to explain the changes in the effect of cinitapride after acute morphine treatment and in morphine tolerant tissues, the changes observed suggest that some of the cinitapride effects could be linked with the peripheral opioid system. PMID:1662171

  20. Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

    PubMed Central

    Mojadadi, Shafi; Jamali, Abbas; Khansarinejad, Behzad; Soleimanjahi, Hoorieh; Bamdad, Taravat

    2009-01-01

    Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte (CTL) activity in the inhibition of herpes simplex virus type 1 (HSV-1) reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-1. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation. PMID:19403060

  1. Evidence for the involvement of excitatory amino acid pathways in the development of precipitated withdrawal from acute and chronic morphine: an in vivo voltammetric study in the rat locus coeruleus.

    PubMed

    Hong, M; Milne, B; Jhamandas, K

    1993-09-24

    Previous studies have demonstrated that activation of excitatory amino acid (EAA) pathways projecting to the locus coeruleus may be involved in the increased firing of locus coeruleus (LC) neurons during opioid withdrawal. Using differential normal pulse voltammetry to monitor catechol oxidation current (CA.OC), an index of neuronal activity in the LC, the role of EAA pathways in naloxone precipitated withdrawal after acute and chronic morphine treatment was examined. Acute morphine treatment (10 micrograms i.c.v.) significantly reduced the CA.OC signal in the LC to 54.3 +/- 3.1% of baseline. Naloxone challenge (1 mg/kg i.v.) completely reversed the morphine effect and produced a significant increase in the CA.OC signal above baseline, peak 145.4 +/- 10.1% of baseline. This naloxone-induced rebound response was attenuated by pretreatment with the EAA receptor antagonists gamma-D-glutamylglycine (DGG) (2, 20, 200 micrograms i.c.v.) and (-)-2-amino-7-phosphonoheptanoic acid (D-APH), but not L-APH (25 micrograms i.c.v.). In chronically morphine-treated rats (25 micrograms/h i.c.v., 5 days), naloxone challenge (1 mg/kg i.v.) produced a significant increase in CA.OC signal, peak 466.5 +/- 112.7% of baseline. This naloxone-induced response was attenuated by pretreatment with DGG (200 micrograms i.c.v.) or D-APH (25 micrograms i.c.v.). To the extent that CA.OC reflects locus coeruleus neuronal activity, the present findings further suggest that increases in locus coeruleus activity during naloxone precipitated withdrawal after both acute and chronic morphine treatment are mediated at least in part by activation of EAA pathways. PMID:8221081

  2. Increased probability of GABA release during withdrawal from morphine.

    PubMed

    Bonci, A; Williams, J T

    1997-01-15

    Opioid receptors located on interneurons in the ventral tegmental area (VTA) inhibit GABA(A)-mediated synaptic transmission to dopamine projection neurons. The resulting disinhibition of dopamine cells in the VTA is thought to play a pivotal role in drug abuse; however, little is known about how this GABAA synapse is affected after chronic morphine treatment. The regulation of GABA release during acute withdrawal from morphine was studied in slices from animals treated for 6-7 d with morphine. Slices containing the VTA were prepared and maintained in morphine-free solutions, and GABAA IPSCs were recorded from dopamine cells. The amplitude of evoked IPSCs and the frequency of spontaneous miniature IPSCs measured in slices from morphine-treated guinea pigs were greater than placebo-treated controls. In addition, activation of adenylyl cyclase, with forskolin, and cAMP-dependent protein kinase, with Sp-cAMPS, caused a larger increase in IPSCs in slices from morphine-treated animals. Conversely, the kinase inhibitors staurosporine and Rp-CPT-cAMPS decreased GABA IPSCs to a greater extent after drug treatment. The results indicate that the probability of GABA release was increased during withdrawal from chronic morphine treatment and that this effect resulted from an upregulation of the cAMP-dependent cascade. Increased transmitter release from opioid-sensitive synapses during acute withdrawal may be one adaptive mechanism that results from prolonged morphine treatment. PMID:8987801

  3. Influence of morphine on the activity of low-threshold visceral mechanoreceptors in cats with acute pericarditis.

    PubMed

    Bałkowiec, A; Kukuła, K; Szulczyk, P

    1994-11-01

    The purpose of this investigation was to test whether morphine (morphinum hydrochloricum) applied to the receptive field of the thoracic visceral afferent fibres modifies their activity. Experiments were performed on chloralose-anaesthetised cats, paralysed and artificially ventilated, in a state of pericarditis that was induced by intrapericardial injection of lambda-carrageenan and kaolin. Resulting acute inflammation was proven histopathologically and documented electrocardiographically. Single afferent fibres with receptive fields in thoracic viscera were dissected from thoracic sympathetic chain (19 fibres), as well as the vagus nerve (9 fibres). All tested fibres transmitted sensory information from the low-threshold mechanoreceptors. As a final result, it was found that morphine (0.001-1.0 mg/ml) when applied locally activates, depending on the dose, afferent fibres as follows: 12 sympathetic afferents (out of 12 tested), and 7 vagal afferents (out of 9 tested). In examining the specificity of morphine action, the preliminary local application of naloxone (1.0 mg/ml) just before morphine, blocked all excitatory responses. The excitatory response was present whether the receptive field was located in the inflammatory area, or outside it, in group III or IV fibres. PMID:7892023

  4. Glutamate receptors in the dorsal hippocampus mediate the acquisition, but not the expression, of conditioned place aversion induced by acute morphine withdrawal in rats

    PubMed Central

    Hou, Yuan-yuan; Liu, Yao; Kang, Shuo; Yu, Chuan; Chi, Zhi-qiang; Liu, Jing-gen

    2009-01-01

    Aim: To evaluate the role of glutamate receptors in the dorsal hippocampus (DH) in the motivational component of morphine withdrawal. Methods: NMDA receptor antagonist D-AP5 (5 μg/0.5 μL per side) or AMPA receptor antagonist NBQX (2 μg/0.5 μL per side) was microinjected into DH of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal were assessed. Results: Preconditioning microinjection of D-AP5 or NBQX into the DH impaired the acquisition of CPA in acute morphine-dependent rats. However, intra-DH microinjection of D-AP5 or NBQX after conditioning but before the testing session had no effect on the expression of CPA. Conclusion: Our results suggest that NMDA and AMPA receptors in the dorsal hippocampus are involved in the acquisition, but not in the expression, of the negative motivational components of acute morphine withdrawal in rats. PMID:19767765

  5. Acute Heart Failure Treatment.

    PubMed

    Levy, Phillip D; Bellou, Abdel

    2013-06-01

    Dyspnea is the predominant symptom for patients with acute heart failure and initial treatment is largely directed towards the alleviation of this. Contrary to conventional belief, not all patients present with fluid overload and the approach to management is rapidly evolving from a solitary focus on diuresis to one that more accurately reflects the complex interplay of underlying cardiac dysfunction and acute precipitant. Effective treatment thus requires an understanding of divergent patient profiles and an appreciation of various therapeutic options for targeted patient stabilization. The key principle within this paradigm is directed management that aims to diminish the work of breathing through situation appropriate ventillatory support, volume reduction and hemodynamic improvement. With such an approach, clinicians can more efficiently address respiratory discomfort while reducing the likelihood of avoidable harm. PMID:24223323

  6. Changes in lymphocyte and macrophage subsets due to morphine and ethanol treatment during a retrovirus infection causing murine AIDS

    SciTech Connect

    Watson, R.R.; Prabhala, R.H.; Darban, H.R.; Yahya, M.D.; Smith, T.L.

    1988-01-01

    The number of lymphocytes of various subsets were not significantly changed by the ethanol exposure except those showing activation markers which were reduced. The percentage of peripheral blood cells showing markers for macrophage functions and their activation were significantly reduced after binge use of ethanol. Ethanol retarded suppression of cells by retroviral infection. However by 25 weeks of infection there was a 8.6% survival in the ethanol fed mice infected with retrovirus which was much less than virally infected controls. Morphine treatment also increased the percentage of cells with markers for macrophages and activated macrophages in virally infected mice, while suppressing them in uninfected mice. The second and third morphine injection series suppressed lymphocyte T-helper and T-suppressor cells, but not total T cells. However, suppression by morphine was significantly less during retroviral disease than suppression caused by the virus only. At 25 weeks of infection 44.8% of morphine treated, infected mice survived.

  7. Morphine Rectal

    MedlinePlus

    Rectal morphine is used to relieve moderate to severe pain. Morphine is in a class of medications called opiate ( ... Rectal morphine comes as a suppository to insert in the rectum. It is usually inserted every 4 hours. Use ...

  8. Effects of oxytocin-related peptides on acute morphine tolerance: opposite actions by oxytocin and its receptor antagonists.

    PubMed

    Kovács, G L; Sarnyai, Z; Izbéki, F; Szabó, G; Telegdy, G; Barth, T; Jost, K; Brtnik, F

    1987-05-01

    The hormonally and behaviorally active nonapeptide oxytocin (OXT), its behaviorally active N-terminal octapeptide desglycinamide9-OXT and Z-prolyl-D-leucine, a synthetic analog of the C-terminal prolyl7-leucine8 sequence, inhibited the development both of a moderate and of a strong tolerance to morphine. N-alpha-Acetyl-(2-0-methyltyrosine)-OXT and (penicillamine1-2-0-methyltyrosine)- lysine8-vasopressin, both OXT receptor antagonists, facilitated the development of a moderate morphine tolerance. The i.c.v. injection of either antagonist prevented the effects of i.c.v. and s.c. OXT treatment on the development of tolerance. The effect of desglycinamide9-OXT, but not that of Z-prolyl-D-leucine was also prevented by N-alpha-acetyl-(2-0-methyltyrosine)-OXT. It is concluded that OXT and desglycinamide9-OXT, but not Z-prolyl-D-leucine, attenuate morphine tolerance by affecting putative oxytocinergic binding sites in the mouse brain. The fact that i.c.v. injection of the receptor antagonist also blocked the effect of s.c. OXT treatment argues in favor of the possibility that a minor proportion of s.c. OXT (or behaviorally active fragments thereof) may reach central nervous system target sites. PMID:3033220

  9. Acute kidney injury in a preterm infant homozygous for the C3435T polymorphism in the ABCB1 gene given oral morphine

    PubMed Central

    Pogliani, Laura; Mameli, Chiara; Cattaneo, Dario; Clementi, Emilio; Meneghin, Fabio; Radice, Sonia; Bruno, Simona; Zuccotti, Gian Vincenzo

    2012-01-01

    A 34-week infant born from a mother with a history of drug abuse developed neonatal abstinence syndrome (NAS) in the first hours of life. Urine drug screening was positive for cocaine and heroin. The infant developed acute kidney injury and bilateral hydronephrosis while receiving oral morphine for control of NAS. Cessation of morphine therapy and urinary catheterization resulted in a rapid and complete resolution of the symptoms. Our patient was homozygous for the C3435T polymorphism in the ABCB1 gene, a polymorphism previously associated with impaired P-glycoprotein activity. We hypothesize that acute renal toxicity was related to accumulation of morphine within urothelial cells due to genetically determined impaired P-glycoprotein activity. PMID:26019822

  10. The combination of morphine and minocycline may be a good treatment for intractable post-herpetic neuralgia.

    PubMed

    Chen, Suchang; Hui, Hui; Zhang, Deren; Xue, Yanzhi

    2010-12-01

    Post-herpetic neuralgia (PHN) is a devastating complication of shingles. The treatment of PHN with traditional pharmaceutical agents has various side effects. Therefore, the treatment of intractable PHN is often very time consuming, mainly because the available treatments often lead to intolerable side effects before the efficient dose can be reached. Opioids such as morphine and oxycodone are the most widely used drugs for the alleviation for severe chronic pain. A number of high quality studies demonstrated that opioids are effective in relieving neuropathic pain including PHN. Yet concerns of misuse, abuse and tolerance of opioids have, however, severely influenced their contribution to neuropathic pain, especially the tolerance that resulted in a loss of drug effect or the necessity for escalating doses to produce pain relief. The glia cells, particularly microglia and astrocytes are thought to play an important role in central sensitization. It is known that activated microglia cells produce NO, cytokines, and cyclooxygenase. All of these chemicals regulate synaptic transmissions in the central nervous system. Additionally, glia modulations showed antiallodynic and antihyperalgesic properties in various experimental pain models. Minocycline, a semisynthetic, second-generation tetracycline can potently inhibit microglial activation and proliferation. Also, the growing body of recent evidence indicates that minocycline attenuates morphine tolerance in neuropathic mice with a mechanism related to microglia. The combination of morphine and minocycline has synergetic effect. This can prevent the development of intractable PHN and attenuate morphine antinociceptive tolerance and further improve the efficacy of morphine and therefore reducing its dosage and side effects. We thereby hypothesize that the combination of morphine and minocycline may produce a duel effect of morphine antinociceptive and minocycline selectively inhibiting the activation of microglia. PMID

  11. Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/KATP signaling pathway

    PubMed Central

    Cunha, Thiago M.; Roman-Campos, Danilo; Lotufo, Celina M.; Duarte, Hugo L.; Souza, Guilherme R.; Verri, Waldiceu A.; Funez, Mani I.; Dias, Quintino M.; Schivo, Ieda R.; Domingues, Andressa C.; Sachs, Daniela; Chiavegatto, Silvana; Teixeira, Mauro M.; Hothersall, John S.; Cruz, Jader S.; Cunha, Fernando Q.; Ferreira, Sergio H.

    2010-01-01

    Morphine is one of the most prescribed and effective drugs used for the treatment of acute and chronic pain conditions. In addition to its central effects, morphine can also produce peripheral analgesia. However, the mechanisms underlying this peripheral action of morphine have not yet been fully elucidated. Here, we show that the peripheral antinociceptive effect of morphine is lost in neuronal nitric-oxide synthase null mice and that morphine induces the production of nitric oxide in primary nociceptive neurons. The activation of the nitric-oxide pathway by morphine was dependent on an initial stimulation of PI3Kγ/AKT protein kinase B (AKT) and culminated in increased activation of KATP channels. In the latter, this intracellular signaling pathway might cause a hyperpolarization of nociceptive neurons, and it is fundamental for the direct blockade of inflammatory pain by morphine. This understanding offers new targets for analgesic drug development. PMID:20147620

  12. The effects of acute and chronic nicotine hydrogen (+)-tartrate administration and subsequent withdrawal on rat liver tryptophan pyrrolase activity and their comparison with those of morphine, phenobarbitone and ethanol.

    PubMed Central

    Badawy, A A; Evans, M

    1975-01-01

    Acute administration of nicotine hydrogen (+)-tartrate enhances the activity of rat liver tryptophan pyrrolase by a hormonal mechanism. Chronic nicotine treatment inhibits, and subsequent withdrawal enhances, the pyrrolase activity. The inhibition during chronic treatment is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. Regeneration of liver NADP+ in vitro and in vivo reverses the inhibition. Chronic nicotine administration increases the liver NADPH concentration. The above effects of nicotine resemble to a remarkable degree those previously shown for morphine, phenobarbitone and ethanol. All effects are compared, and their possible significance in relation to drug dependence is discussed. PMID:989

  13. Morphine for the Treatment of Pain in Sickle Cell Disease

    PubMed Central

    Ballas, Samir K.

    2015-01-01

    Pain is a hallmark of sickle cell disease (SCD) and its treatment remains challenging. Opioids are the major family of analgesics that are commonly used for treating severe pain. However, these are not always effective and are associated with the liabilities of their own. The pharmacology and multiorgan side effects of opioids are rapidly emerging areas of investigation, but there remains a scarcity of clinical studies. Due to opioid-induced endothelial-, mast cell-, renal mesangial-, and epithelial-cell-specific effects and proinflammatory as well as growth influencing signaling, it is likely that when used for analgesia, opioids may have organ specific pathological effects. Experimental and clinical studies, even though extremely few, suggest that opioids may exacerbate existent organ damage and also stimulate pathologies of their own. Because of the recurrent and/or chronic use of large doses of opioids in SCD, it is critical to evaluate the role and contribution of opioids in many complications of SCD. The aim of this review is to initiate inquiry to develop strategies that may prevent the inadvertent effect of opioids on organ function in SCD, should it occur, without compromising analgesia. PMID:25654130

  14. Antinociceptive effect of palm date spathe hydroalcoholic extract on acute and chronic pain in mice as compared with analgesic effect of morphine and diclofenac

    PubMed Central

    Peyghambari, Fatemeh; Dashti-Rahmatabadi, Mohammad Hossein; Rozabadi, Mansooreh Dehghanfi; Rozabadi, Razieh Dehghanfi; Rozabadi, Fatemeh Dehghanfi; Pangalizadeh, Mohammadesmaeil; Dehghanimohammadabadi, Narges

    2015-01-01

    Backgrounds: In Persian traditional medicine, palm date spathe (PDS) is introduced as an analgesic. Therefore, this study was designed to investigate the analgesic effect of hydroalcoholic extract of PDS on acute and chronic pain in mice in comparison with diclofenac and morphine. Materials and Methods: In this study, which was conducted in summer 2014, 220 male mice (20–30 g) were randomly divided into two categories, each consists of 11 groups as follows: A normal control group, a solvent (Tween 80) control group, 3 morphine positive control groups (2, 4 and 8 mg/kg), 3 diclofenac positive control groups (10, 20 and 30 mg/kg), and 3 main experimental PDS groups (2, 20, and 200 mg/kg). Hot plate was applied on animals in one category and writing test on the other category to assess acute and chronic pain, respectively. Results: In the writing test, the average writing time and number of animals receiving a maximum dosage of morphine, diclofenac, and PDS were significantly less than the control group. In the hot plate test, only groups receiving different doses of morphine at different time points and those received 30 mg/kg diclofenac at 15 min after the intervention showed significant difference with the control group. Conclusion: 200 mg/kg extract of PDS, revealed a significant analgesic effect on chronic pain, but it did not show any analgesic effect on acute pain. PMID:26693469

  15. Ellagic acid enhances morphine analgesia and attenuates the development of morphine tolerance and dependence in mice.

    PubMed

    Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Ghorbanzadeh, Behnam

    2014-10-15

    According to our previous study, ellagic acid has both dose-related central and peripheral antinociceptive effect through the opioidergic and l-arginine-NO-cGMP-ATP sensitive K(+) channel pathways. In the present study, the systemic antinociceptive effects of ellagic acid in animal models of pain, and functional interactions between ellagic acid and morphine in terms of analgesia, tolerance and dependence were investigated. Ellagic acid (1-30mg/kg; i.p.) showed significant and dose-dependent antinociceptive effects in the acetic acid-induced writhing test. Intraperitoneal ellagic acid acutely interacted with morphine analgesia in a synergistic manner in this assay. Ellagic acid (1-10mg/kg; i.p.) also exerted analgesic activity in the hot-plate test. Pre-treatment with naloxone (1mg/kg; i.p.) significantly reversed ellagic acid, morphine as well as ellagic acid-morphine combination-induced antinociceptin in these two tests. More importantly, when co-administered with morphine, ellagic acid (1-10mg/kg) effectively blocked the development of tolerance to morphine analgesia in the hot-plate test. Likewise, ellagic acid dose-dependently prevented naloxone-precipitated withdrawal signs including jumping and weight loss. Ellagic acid treatment (1-30mg/kg; i.p.) had no significant effect on the locomotion activity of animals using open-field task. Therefore, these results showed that ellagic acid has notable systemic antinociceptive activity for both tonic and phasic pain models. Altogether, ellagic acid might be used in pain relief alone or in combination with opioid drugs because of enhancing morphine analgesia and preventing morphine-induced tolerance to analgesia and dependence. PMID:25179576

  16. Endogenous Cholinergic Neurotransmission Contributes to Behavioral Sensitization to Morphine

    PubMed Central

    Bajic, Dusica; Soiza-Reilly, Mariano; Spalding, Allegra L.; Berde, Charles B.; Commons, Kathryn G.

    2015-01-01

    Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg), a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter) in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg) dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg. PMID:25647082

  17. Effect of interaction between acute administration of morphine and cannabinoid compounds on spontaneous excitatory and inhibitory postsynaptic currents of magnocellular neurons of supraoptic nucleus

    PubMed Central

    Yousefpour, Mitra; Naderi, Nima; Motamedi, Fereshteh

    2016-01-01

    Objective(s): Opioids and cannabinoids are two important compounds that have been shown to influence the activity of magnocellular neurons (MCNs) of supraoptic nucleus (SON). The interaction between opioidergic and cannabinoidergic systems in various structures of the brain and spinal cord is now well established, but not in the MCNs of SON. Materials and methods: In this study, whole cell patch clamp recording of neurons in rat brain slice was used to investigate the effect of acute morphine and cannabinoid administration on spontaneous inhibitory and excitatory spostsynaptic currents (sIPSCs and sEPSCs) in MCNs. Results: Bath application of morphine produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency. In contrast, bath application of URB597 (fatty acid amide hydrolase (FAAH) inhibitor) produced a decrease in sEPSCs frequency but an increase in sIPSCs frequency. WIN55212-2 (cannabinoid receptor agonist) decreased both sIPSCs and sEPSCs frequencies of MCNs. Co-application of morphine and URB597 attenuated the effect of morphine on MCNs. Conclusion: Taken together, these data indicated that at the cellular level, pharmacological augmentation of endocannabinoids could attenuate morphine effects on MCNs. PMID:27482350

  18. Effective management of intractable neuropathic pain using an intrathecal morphine pump in a patient with acute transverse myelitis

    PubMed Central

    Wu, Wei-Ting; Huang, Yu-Hui; Chen, Der-Cherng; Huang, Yu-Hsuan; Chou, Li-Wei

    2013-01-01

    Transverse myelitis is a rare inflammatory myelopathy characterized by loss of motor and sensory function below the affected level of the spinal cord, and causes neurogenic bowel and bladder. Occasionally, it also causes neuropathic pain with spasticity. Traditional therapies for neuropathic pain are multiple, including multimodal analgesic regimens, antiepileptic or antidepressant medications, opioids, sympathetic blocks, and spinal cord stimulation. Persistent neuropathic pain can cause emotional distress by affecting sleep, work, recreation, and emotional well-being. Here we report the case of a patient suffering from intractable neuropathic pain following acute transverse myelitis that was not relieved by combinations of nonsteroidal anti-inflammatory, anti-epileptic, antidepressant, and opioid medications, or by acupuncture. Implantation of an intrathecal morphine pump controlled the pain successfully without side effects, and enabled the patient to embark on intensive rehabilitation. The patient’s muscle strength has improved significantly and the patient may soon be able to use a walker with minimal assistance. PMID:23935366

  19. Distinct interactions of cannabidiol and morphine in three nociceptive behavioral models in mice.

    PubMed

    Neelakantan, Harshini; Tallarida, Ronald J; Reichenbach, Zachary W; Tuma, Ronald F; Ward, Sara J; Walker, Ellen A

    2015-04-01

    Cannabinoid and opioid agonists can display overlapping behavioral effects and the combination of these agonists is known to produce enhanced antinociception in several rodent models of acute and chronic pain. The present study investigated the antinociceptive effects of the nonpsychoactive cannabinoid, cannabidiol (CBD) and the µ-opioid agonist morphine, both alone and in combination, using three behavioral models in mice, to test the hypothesis that combinations of morphine and CBD would produce synergistic effects. The effects of morphine, CBD, and morphine/CBD combinations were assessed in the following assays: (a) acetic acid-stimulated stretching; (b) acetic acid-decreased operant responding for palatable food; and (c) hot plate thermal nociception. Morphine alone produced antinociceptive effects in all three models of acute nociception, whereas CBD alone produced antinociception only in the acetic acid-stimulated stretching assay. The nature of the interactions between morphine and CBD combinations were assessed quantitatively based on the principle of dose equivalence. Combinations of CBD and morphine produced synergistic effects in reversing acetic acid-stimulated stretching behavior, but subadditive effects in the hot plate thermal nociceptive assay and the acetic acid-decreased operant responding for palatable food assay. These results suggest that distinct mechanisms of action underlie the interactions between CBD and morphine in the three different behavioral assays and that the choice of appropriate combination therapies for the treatment of acute pain conditions may depend on the underlying pain type and stimulus modality. PMID:25485642

  20. Dopamine-dependent responses to morphine depend on glucocorticoid receptors

    PubMed Central

    Marinelli, Michela; Aouizerate, Bruno; Barrot, Michel; Le Moal, Michel; Piazza, Pier Vincenzo

    1998-01-01

    Previous work has shown that glucocorticoid hormones facilitate the behavioral and dopaminergic effects of morphine. In this study we examined the possible role in these effects of the two central corticosteroid receptor types: mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). To accomplish this, specific antagonists of these receptors were infused intracerebroventricularly and 2 hr later we measured: (i) locomotor activity induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity induced by an infusion of morphine (1 μg per side) into the ventral tegmental area, which is a dopamine-dependent behavioral response to morphine; (iii) morphine-induced dopamine release in the nucleus accumbens, a dopaminergic projection site mediating the locomotor and reinforcing effects of drugs of abuse. Blockade of MRs by spironolactone had no significant effects on locomotion induced by systemic morphine. In contrast, blockade of GRs by either RU38486 or RU39305, which is devoid of antiprogesterone effects, reduced the locomotor response to morphine, and this effect was dose dependent. GR antagonists also reduced the locomotor response to intraventral tegmental area morphine as well as the basal and morphine-induced increase in accumbens dopamine, as measured by microdialysis in freely moving rats. In contrast, spironolactone did not modify dopamine release. In conclusion, glucocorticoids, via GRs, facilitate the dopamine-dependent behavioral effects of morphine, probably by facilitating dopamine release. The possibility of decreasing the behavioral and dopaminergic effects of opioids by an acute administration of GR antagonists may open new therapeutic strategies for treatment of drug addiction. PMID:9636221

  1. Tolerance to hyperthermia produced by morphine in rat.

    PubMed

    Mucha, R F; Kalant, H; Kim, C

    1987-01-01

    The present study addressed the prevailing notion that the rat develops tolerance only to the hypothermic effect of morphine and not to its hyperthermic effect. Rectal temperatures were measured at different intervals after various test doses of morphine in rats that had been rendered tolerant to morphine antinociception, by daily intraperitoneal injections of 0, 20, or 200 mg/kg morphine, and dependent, as seen by naloxone-produced loss of body weight. The well-known tolerance to the hypothermic effect was confirmed by changes in the dose-response curves for latency to peak hyperthermic response. In the falling arm of the test dose time/effect curve, consistent, clear decreases in morphine hyperthermia were seen. These decreases were proportional to the chronic treatment dose, and occurred in a normal test environment, where acute hypothermic effects were produced by morphine at short test intervals, and in a warm test environment, where no hypothermia was seen. Similar effects were noted when the data were analyzed in terms of area under the time/effect curve for hyperthermia. In the morphine-treated animals, decreased hyperthermia was seen despite serum morphine levels at the time of testing being up to twice as high as those in control rats. It was concluded that substantial tolerance develops to hyperthermia produced by opiates in rats. The previous difficulty in seeing this effect is discussed in regard to the probability that, in naive rats, the effect of morphine shortly after administration of a test dose reflects a summation of two opposing, acute thermic effects. The findings challenge the view that tolerance develops only to the depressant, and not to the excitatory, effects of opiates. PMID:3114798

  2. Commonly Used Acute Migraine Treatments

    MedlinePlus

    ... that make headaches worse (or lead to decreased responsiveness to other drug therapies) Patient preference Goals of ... Reduce frequency, severity, and duration of attacks Improve responsiveness to treatment of acute attacks Reduce level of ...

  3. Formation of aversive memories associated with conditioned drug withdrawal requires BDNF expression in the amygdala in acute morphine-dependent rats

    PubMed Central

    Ju, Yun-yue; Long, Jian-dong; Liu, Yao; Liu, Jing-gen

    2015-01-01

    Aim: Brain-derived neurotrophic factor (BDNF) plays an important role in learning and memory in multiple brain areas. In the present study, we investigated the roles of BDNF in aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats. Methods: Conditioned place aversion (CPA) was induced in male SD rats exposed to a single dose of morphine (10 mg/kg, sc) followed by naloxone (0.3 mg/kg, sc). In some rats, BDNF receptor antagonist K252a (8.5 ng per side) or BDNF scavenger TrkB-FC (0.65 μg per side) was bilaterally microinjected into amygdala before naloxone injection. BDNF mRNA and protein expression levels in amygdala were detected after the behavior testing. Results: CPA behavior was induced in rats by the naloxone-precipitated morphine withdrawal, which was accompanied by significantly increased levels of BDNF mRNA and protein in the amygdala. Bilateral microinjection of TrkB-FC or K252a into the amygdala completely blocked CPA behavior in the rats. Conclusion: Formation of aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats requires BDNF expression in the amygdala. PMID:26567727

  4. Morphine Oral

    MedlinePlus

    ... relieve moderate to severe pain. Morphine extended-release tablets and capsules are only used to relieve severe ( ... use of other pain medications. Morphine extended-release tablets and capsules should not be used to treat ...

  5. Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin.

    PubMed

    Hogan, Dale; Baker, Alyssa L; Morón, Jose A; Carlton, Susan M

    2013-11-01

    Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal pain sensitivity-hyperalgesia and/or allodynia. We hypothesized that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia and tested this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected intraperitoneally with escalating doses of morphine (5, 8, 10, 15 mg/kg) or saline every 12 hours for 48 hours and killed approximately 12 hours after the last injection. Receptive fields of nociceptors were tested for mechanical, heat, and cold sensitivity. Activity was also measured during an initial 2-minute period and during 5-minute periods between stimuli. Aberrant activity was common in fibers from morphine-treated mice but rare in saline-treated mice. Resting background activity was elevated in C-fibers from morphine-treated mice. Both C- and Aδ-fibers had afterdischarge in response to mechanical, heat, and/or cold stimulation of the skin as well as spontaneous, unevoked activity. Compared to saline, morphine treatment increased the proportion of fibers displaying polymodal rather than mechanical-only responses. A significant increase in Aδ-mechanoreceptive fibers responding to cold accounted for most of this change. In agreement with this, morphine-treated mice showed increased sensitivity in the cold tail flick test. In morphine-treated mice, aberrant activity and hyperexcitability of nociceptors could contribute to increased pain sensitivity. Importantly, this activity is likely driving central sensitization, a phenomenon contributing to abnormal sensory processing and chronic pain. If similar changes occur in human patients, aberrant nociceptor activity is likely to be interpreted as pain and could contribute to opioid-induced hyperalgesia. PMID:23711478

  6. Comparison of (+)- and (−)-Naloxone on the Acute Psychomotor-Stimulating Effects of Heroin, 6-Acetylmorphine, and Morphine in Mice

    PubMed Central

    Andersen, Jannike Mørch; Boix, Fernando; Bergh, Marianne Skov-Skov; Vindenes, Vigdis; Rice, Kenner C.; Huestis, Marilyn A.; Mørland, Jørg

    2016-01-01

    Toll-like receptor 4 (TLR4) signaling is implied in opioid reinforcement, reward, and withdrawal. Here, we explored whether TLR4 signaling is involved in the acute psychomotor-stimulating effects of heroin, 6-acetylmorphine (6-AM), and morphine as well as whether there are differences between the three opioids regarding TLR4 signaling. To address this, we examined how pretreatment with (+)-naloxone, a TLR4 active but opioid receptor (OR) inactive antagonist, affected the acute increase in locomotor activity induced by heroin, 6-AM, or morphine in mice. We also assessed the effect of pretreatment with (−)-naloxone, a TLR4 and OR active antagonist, as well as the pharmacokinetic profiles of (+) and (−)-naloxone in the blood and brain. We found that (−)-naloxone reduced acute opioid-induced locomotor activity in a dose-dependent manner. By contrast, (+)-naloxone, administered in doses assumed to antagonize TLR4 but not ORs, did not affect acute locomotor activity induced by heroin, 6-AM, or morphine. Both naloxone isomers exhibited similar concentration versus time profiles in the blood and brain, but the brain concentrations of (−)-naloxone reached higher levels than those of (+)-naloxone. However, the discrepancies in their pharmacokinetic properties did not explain the marked difference between the two isomers’ ability to affect opioid-induced locomotor activity. Our results underpin the importance of OR activation and do not indicate an apparent role of TLR4 signaling in acute opioid-induced psychomotor stimulation in mice. Furthermore, there were no marked differences between heroin, 6-AM, and morphine regarding involvement of OR or TLR4 signaling. PMID:27278234

  7. Acute Migraine Treatment in Adults.

    PubMed

    Becker, Werner J

    2015-06-01

    There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office-based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID-triptan combinations, dihydroergotamine, non-opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti-emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence-based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication

  8. Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

    PubMed

    Shibasaki, Masahiro; Ishii, Kazunori; Masukawa, Daiki; Ando, Koji; Ikekubo, Yuiko; Ishikawa, Yutori; Shibasaki, Yumiko; Mori, Tomohisa; Suzuki, Tsutomu

    2014-09-01

    Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor. PMID:24930812

  9. Combined effect of fluconazole and thymosin alpha 1 on systemic candidiasis in mice immunosuppressed by morphine treatments.

    PubMed Central

    di Francesco, P; Gaziano, R; Casalinuovo, I A; Belogi, L; Palamara, A T; Favalli, C; Garaci, E

    1994-01-01

    Treatment of systemic infection with Candida albicans with a combination of an antifungal agent (i.e. fluconazole) and a thymus-derived immunostimulant (i.e. thymosin alpha 1 (T alpha 1)) in mice immunosuppressed by morphine treatments was investigated. In normal mice, fluconazole given after infection with 10(6) C. albicans cells was more effective than in mice treated with morphine. Combination treatment with fluconazole and T alpha 1 prolonged survival and reduced the fungal burden in the kidneys of immunosuppressed mice. We also investigated the influence of this combined treatment on killing properties of polymorphonuclear leucocytes (PMN) and natural killer (NK) cell activity, inhibited by morphine administrations. Treatment with T alpha 1 or fluconazole as single agents promoted a recovery of normal NK cell activity and intracellular killing of C. albicans by PMN, while the combination significantly increased both of these responses, probably through the modulation of lymphokine production. Our data suggest that the additive effect of T alpha 1 and fluconazole is due to a direct antifungal action and activation of the immunocompetence. PMID:8082290

  10. Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments

    PubMed Central

    Elhabazi, K; Trigo, JM; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, JJ; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

    2012-01-01

    BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. PMID:21718302

  11. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  12. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  13. Acute treatment of migraine headaches.

    PubMed

    Taylor, Frederick R

    2010-04-01

    Optimum acute treatment of migraine requires prevention of headache as a top priority. Recognition of the multitude of migraine presentations, the frequency of total headache attacks, and number of days of headache disability are critical. Successful treatment requires excellent patient-clinician communication enhancing confidence and mutual trust based on patient needs and preferences. Optimum management of acute migraine nearly always requires pharmacologic treatment for rapid resolution. Migraine-specific triptans, dihydroergotamine, and several antiinflammatories have substantial empirical clinical efficacy. Older nonspecific drugs, particularly butalbital and opioids, contribute to medication overuse headache and are to be avoided. Clinicians should utilize evidence-based acute migraine-specific therapy stressing the imperative acute treatment goal of early intervention, but not too often with the correct drug, formulation, and dose. This therapy needs to provide cost-effective fast results, meaningful to the patient while minimizing the need for additional drugs. Migraine-ACT evaluates 2-hour pain freedom with return to normal function, comfort with treatment, and consistency of response. Employ a thoroughly educated patient, formulary, testimonials, stratification, and rational cotherapy against the race to central sensitization for optimum outcomes. PMID:20352584

  14. (1) H-nuclear magnetic resonance-based metabonomic analysis of brain in rhesus monkeys with morphine treatment and withdrawal intervention.

    PubMed

    Deng, Yi; Bu, Qian; Hu, Zhengtao; Deng, Pengchi; Yan, Guangyan; Duan, Jiachuan; Hu, Chunyan; Zhou, Jiaqing; Shao, Xue; Zhao, Jinxuan; Li, Yan; Zhu, Ruiming; Zhao, Yinglan; Cen, Xiaobo

    2012-11-01

    Comprehensive cerebral metabolites involved in morphine dependence have not been well explored. To gain a better understanding of morphine dependence and withdrawal therapy in a model highly related to humans, metabolic changes in brain hippocampus and prefrontal cortex (PFC) of rhesus monkeys were measured by (1) H-nuclear magnetic resonance spectroscopy, coupled with partial least squares and orthogonal signal correction analysis. The results showed that concentrations of myoinositol (M-Ins) and taurine were significantly reduced, whereas lactic acid was increased in hippocampus and PFC of morphine-dependent monkeys. Phosphocholine and creatine increased in PFC but decreased in hippocampus after chronic treatment of morphine. Moreover, N-acetyl aspartate (NAA), γ-aminobutyric acid, glutamate, glutathione, methionine, and homocysteic acid also changed in these brain regions. These results suggest that chronic morphine exposure causes profound disturbances of neurotransmitters, membrane, and energy metabolism in the brain. Notably, morphine-induced dysregulations in NAA, creatine, lactic acid, taurine, M-Ins, and phosphocholine were clearly reversed after intervention with methadone or clonidine. Our study highlights the potential of metabolic profiling to enhance our understanding of metabolite alteration and neurobiological actions associated with morphine addiction and withdrawal therapy in primates. PMID:22847893

  15. Quality of life under oxycodone/naloxone, oxycodone, or morphine treatment for chronic low back pain in routine clinical practice

    PubMed Central

    Ueberall, Michael A; Eberhardt, Alice; Mueller-Schwefe, Gerhard HH

    2016-01-01

    Objective To compare the quality of life of patients with moderate-to-severe chronic low back pain under treatment with the WHO-step III opioids oxycodone/naloxone, oxycodone, or morphine in routine clinical practice. Study design Prospective, 12-week, randomized, open-label, blinded end-point study in 88 medical centers in Germany. Patients and methods A total of 901 patients requiring around-the-clock pain treatment with a WHO-step III opioid were randomized to either morphine, oxycodone, or oxycodone/naloxone (1:1:1). Changes from baseline to week 12 in quality of life were assessed using different validated tools (EuroQoL-5 Dimensions [EQ-5D], Short Form 12 [SF-12], quality of life impairment by pain inventory [QLIP]). Results EQ-5D weighted index scores significantly improved over the 12-week treatment period under all three opioids (P<0.001) with significantly greater improvements under oxycodone/naloxone (65.2% vs 49.6% for oxycodone and 48.2% for morphine, P<0.001). The proportion of patients without EQ-5D complaints was also significantly higher under oxycodone/naloxone (P<0.001). Although quality of life ratings with the QLIP inventory showed significant improvements in all the three treatment arms, improvements were significantly higher under oxycodone/naloxone than under oxycodone and morphine (P<0.001): 90.7% of all oxycodone/naloxone patients achieved ≥30% improvements in quality of life, 72.8% had ≥50%, and 33.2% ≥70% improvements. Similarly, both physical and mental SF-12 component scores showed significantly greater improvements under oxycodone/naloxone with both scores close to the German population norm after 12 weeks. Conclusion Treatment with morphine, oxycodone, or oxycodone/naloxone under routine daily practice conditions significantly improved state of health and quality of life of patients with moderate-to-severe low back pain over a 12-week treatment period. Comparison between the treatment groups showed significantly greater

  16. Acute treatment of atrial fibrillation.

    PubMed

    Kowey, P R; Marinchak, R A; Rials, S J; Filart, R A

    1998-03-12

    Atrial fibrillation (AFib) is a common clinical entity, responsible for significant morbidity and mortality, but it also accounts for a large percentage of healthcare dollar expenditures. Efforts to treat this arrhythmia in the past have focused on subacute antithrombotic therapy and eventually use of antiarrhythmic drugs for maintenance of sinus rhythm. However, there has been a growing interest in the concept of acute electrical and pharmacologic conversion. This treatment strategy has a number of benefits, including immediate alleviation of patient symptoms, avoidance of antithrombotic therapy, and prevention of electrophysiologic remodeling, which is thought to contribute to the perpetuation of the arrhythmia. There is also increasing evidence that this is a cost-effective strategy in that it may obviate admission to the hospital and the cost of long-term therapy. This article represents a summary of the treatments that may be used acutely to control the ventricular response to AFib, prevent thromboembolic events, and provide for acute conversion either pharmacologically or electrically. It includes information on modalities that are currently available and those that are under active development. We anticipate that an active, acute treatment approach to AFib and atrial flutter will become the therapeutic norm in the next few years, especially as the benefits of these interventions are demonstrated in clinical trials. PMID:9525568

  17. [Treatment of chronic pain of oncologic origin with epidural or intrathecal morphine administered by continuous or programmable flow implanted pumps].

    PubMed

    Rodríguez López, M J; de la Torre Liébanas, M; Sánchez-Guijo Bernal, J J; Muñoz de la Guardia, J L

    1990-01-01

    We have treated a total of 40 patients who presented chronic pain secondary to a neoplastic condition; the patients were treated with morphine in a continuous perfusion by means of an implanted perfusion pump. The route used was the epidural route in seven patients and the intrathecal route in the remaining 33 patients. In 22 patients, the implanted pump was the continuous flow Infusaid model and in the remaining 18, the programmable flow Synchromed (Medtronic) model. The daily dose of morphine ranged from 2.4 mg to 48 mg and maximum perfusion period was 19 months. Main complications were displacement of the catheter and rejection of perfusion system. Despite its high prize, we believe that such treatment system should be considered because of the quality of life improvement of the patients. PMID:2098877

  18. Hypothalamic-pituitary-adrenal activity and pro-opiomelanocortin mRNA levels in the hypothalamus and pituitary of the rat are differentially modulated by acute intermittent morphine with or without water restriction stress.

    PubMed

    Zhou, Y; Spangler, R; Maggos, C E; Wang, X M; Han, J S; Ho, A; Kreek, M J

    1999-11-01

    Acute administration of morphine stimulates the secretion of hypothalamic-pituitary-adrenal (HPA) hormones, ACTH, beta-endorphin and corticosterone in the rat. In this study we investigated the effects of repeated multiple-dose morphine on HPA activity under two different conditions: without or with water restriction stress. Rats received six intermittent injections of morphine (6.25 mg/kg per injection, s.c.) every 2 h and were killed 30 min after the last injection. The results were as follows. (1) Morphine significantly elevated plasma ACTH and corticosterone levels; water restriction also significantly increased ACTH secretion, but with no significant increase of plasma corticosterone levels. In contrast, rats treated with morphine under the water restriction condition failed to show any increases of either ACTH or corticosterone levels. (2) Morphine did not change pro-opiomelanocortin (POMC) mRNA levels in the anterior pituitary; whereas water restriction significantly increased the POMC mRNA levels. The water restriction-induced increases of POMC mRNA in the anterior pituitary were absent in the rats which received morphine. (3) Morphine significantly increased POMC mRNA levels in the hypothalamus; water restriction had no effect. The morphine-induced increases in POMC mRNA in the hypothalamus were absent in the rat under the water restriction condition. These findings, that the effects of morphine on HPA activation or POMC mRNA expression depend on the presence of stress, suggest a counter-regulatory role of opiates on a stress response and opioid gene expression. PMID:10556776

  19. Acute intermittent morphine increases preprodynorphin and kappa opioid receptor mRNA levels in the rat brain.

    PubMed

    Wang, X M; Zhou, Y; Spangler, R; Ho, A; Han, J S; Kreek, M J

    1999-03-20

    We determined the effects of morphine on mRNA levels for the opioid ligands preprodynorphin (PPD) and preproenkephalin (PPE) and the kappa opioid receptor (KOR). Rats received six injections of morphine (6.25 mg/kg/injection) every 2 h, and were sacrificed 30 min later. mRNA levels were measured in brain tissue after removal of the cortex, cerebellum and brainstem. There were increases in PPD and KOR mRNA levels (P<0.05 and P<0.005, respectively), with no alteration of PPE. These alterations in the kappa/dynorphin system may counter morphine-induced effects on the brain. PMID:10095091

  20. Single-sweep spectral analysis of contact heat evoked potentials: a novel approach to identify altered cortical processing after morphine treatment

    PubMed Central

    Hansen, Tine M; Graversen, Carina; Frøkjær, Jens B; Olesen, Anne E; Valeriani, Massimiliano; Drewes, Asbjørn M

    2015-01-01

    Aims The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single-sweep characteristics to identify alterations induced by morphine. Methods In a crossover study 15 single-sweep CHEPs were analyzed from 62 electroencephalography electrodes in 26 healthy volunteers before and after administration of morphine or placebo. Each sweep was decomposed by a continuous wavelet transform to obtain normalized spectral indices in the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–32 Hz) and gamma (32–80 Hz) bands. The average distribution over all sweeps and channels was calculated for the four recordings for each volunteer, and the two recordings before treatments were assessed for reproducibility. Baseline corrected spectral indices after morphine and placebo treatments were compared to identify alterations induced by morphine. Results Reproducibility between baseline CHEPs was demonstrated. As compared with placebo, morphine decreased the spectral indices in the delta and theta bands by 13% (P = 0.04) and 9% (P = 0.007), while the beta and gamma bands were increased by 10% (P = 0.006) and 24% (P = 0.04). Conclusion The decreases in the delta and theta band are suggested to represent a decrease in the pain specific morphology of the CHEPs, which indicates a diminished pain response after morphine administration. Hence, assessment of spectral indices in single-sweep CHEPs can be used to study cortical mechanisms induced by morphine treatment. PMID:25556985

  1. Impact of the Timing of Morphine Administration on Lipopolysaccharide-Mediated Lethal Endotoxic Shock in Mice.

    PubMed

    Fukada, Tomoko; Kato, Hidehito; Ozaki, Makoto; Yagi, Junji

    2016-05-01

    Sepsis is a serious condition related to systemic inflammation, organ dysfunction, and organ failure. It is a subset of the cytokine storm caused by dysregulation of cytokine production. Morphine influences the severity of infection in vivo and in vitro because it regulates cytokine production. We investigated the immunological function of morphine using a mouse model of septic shock. We treated mice with α-galactosylceramide (2 μg/mouse) to induce lethal endotoxic shock following a challenge with lipopolysaccharide (LPS, 1.5 μg/mouse). This model represents acute lung injury and respiratory failure, and reflects the clinical features of severe septic shock. We evaluated the effect of the timing of morphine (0.8 mg/mouse) administration on the survival rate, cytokine production in vivo, and histological changes of mice with LPS-mediated lethal endotoxic shock. Morphine treatment before LPS challenge suppressed lethal endotoxic shock. In contrast, when we administered after LPS, morphine exacerbated lethal endotoxic shock; hematoxylin and eosin staining revealed a marked increase in the accumulation of infiltrates comprising polymorphonuclear leukocytes and mononuclear cells in the lung; and Elastica van Gieson staining revealed the destruction of alveoli. The plasma levels of tumor necrosis factor-α, interferon-γ, monocyte-chemotactic protein-1, and interleukin-12 in the group treated with morphine after LPS challenge were higher than those treated with morphine before LPS challenge. In conclusion, one of the factors that determine whether morphine exacerbates or inhibits infection is the timing of its administration. Morphine treatment before shock improved the survival rate, and morphine treatment after shock decreased the rate of survival. PMID:26682949

  2. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

    PubMed Central

    Chen, Hwei-Hsien; Chiang, Yao-Chang; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-kang; Chen, Shao-Tsu

    2015-01-01

    Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders. PMID:25834439

  3. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse

    PubMed Central

    Liu, Yuchen; Li, Dameng; Liu, Zhengya; Zhou, Yu; Chu, Danping; Li, Xihan; Jiang, Xiaohong; Hou, Dongxia; Chen, Xi; Chen, Yuda; Yang, Zhanzhao; Jin, Ling; Jiang, Waner; Tian, Chenfei; Zhou, Geyu; Zen, Ke; Zhang, Junfeng; Zhang, Yujing; Li, Jing; Zhang, Chen-Yu

    2015-01-01

    Cell-derived exosomes have been demonstrated to be efficient carriers of small RNAs to neighbouring or distant cells, highlighting the preponderance of exosomes as carriers for gene therapy over other artificial delivery tools. In the present study, we employed modified exosomes expressing the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface to deliver opioid receptor mu (MOR) siRNA into the brain to treat morphine addiction. We found that MOR siRNA could be efficiently packaged into RVG exosomes and was associated with argonaute 2 (AGO2) in exosomes. These exosomes efficiently and specifically delivered MOR siRNA into Neuro2A cells and the mouse brain. Functionally, siRNA-loaded RVG exosomes significantly reduced MOR mRNA and protein levels. Surprisingly, MOR siRNA delivered by the RVG exosomes strongly inhibited morphine relapse via the down-regulation of MOR expression levels. In conclusion, our results demonstrate that targeted RVG exosomes can efficiently transfer siRNA to the central nervous system and mediate the treatment of morphine relapse by down-regulating MOR expression levels. Our study provides a brand new strategy to treat drug relapse and diseases of the central nervous system. PMID:26633001

  4. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse.

    PubMed

    Liu, Yuchen; Li, Dameng; Liu, Zhengya; Zhou, Yu; Chu, Danping; Li, Xihan; Jiang, Xiaohong; Hou, Dongxia; Chen, Xi; Chen, Yuda; Yang, Zhanzhao; Jin, Ling; Jiang, Waner; Tian, Chenfei; Zhou, Geyu; Zen, Ke; Zhang, Junfeng; Zhang, Yujing; Li, Jing; Zhang, Chen-Yu

    2015-01-01

    Cell-derived exosomes have been demonstrated to be efficient carriers of small RNAs to neighbouring or distant cells, highlighting the preponderance of exosomes as carriers for gene therapy over other artificial delivery tools. In the present study, we employed modified exosomes expressing the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface to deliver opioid receptor mu (MOR) siRNA into the brain to treat morphine addiction. We found that MOR siRNA could be efficiently packaged into RVG exosomes and was associated with argonaute 2 (AGO2) in exosomes. These exosomes efficiently and specifically delivered MOR siRNA into Neuro2A cells and the mouse brain. Functionally, siRNA-loaded RVG exosomes significantly reduced MOR mRNA and protein levels. Surprisingly, MOR siRNA delivered by the RVG exosomes strongly inhibited morphine relapse via the down-regulation of MOR expression levels. In conclusion, our results demonstrate that targeted RVG exosomes can efficiently transfer siRNA to the central nervous system and mediate the treatment of morphine relapse by down-regulating MOR expression levels. Our study provides a brand new strategy to treat drug relapse and diseases of the central nervous system. PMID:26633001

  5. Social influences on morphine sensitization in adolescent females.

    PubMed

    Hofford, Rebecca S; Roberts, Kris W; Wellman, Paul J; Eitan, Shoshana

    2010-08-01

    We recently observed that social interactions influence morphine responsiveness in adolescent males. Given sex-related differences in both social interactions and responses to morphine, the present study examines social influences on morphine sensitization in adolescent female mice. Four experimental groups were examined: (1) morphine-treated mice (twice daily, 10-40 mg/kg, s.c.) housed physically and visually separated from saline-treated mice ('morphine only'), (2) morphine-treated mice housed together with saline-treated mice ('morphine cage-mates (of saline)'), (3) saline-treated mice housed together with morphine-treated mice ('saline cage-mates (of morphine)'), and (4) saline-treated mice housed physically and visually separated from morphine-treated mice ('saline only'). Following the treatment period, mice were tested individually for their locomotor response to 20 mg/kg morphine (s.c.). There were no significant differences in morphine-induced hyper-locomotion between saline only and saline cage-mates (of morphine) female adolescent mice. Notably, morphine only mice exhibited significantly greater morphine sensitization as compared to morphine cage-mates (of saline). Thus, this study demonstrates social influences on morphine sensitization in adolescent females. Drug use during early adolescence is a key predictor of later drug abuse and dependence during adulthood. Thus, understanding the specific vulnerabilities to drug use in this age group may represent a first step in helping develop more effective treatment programs. PMID:20456874

  6. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients

    PubMed Central

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200 mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20 mg and 30 mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic. PMID:26617438

  7. AN IL-1 RECEPTOR ANTAGONIST BLOCKS A MORPHINE-INDUCED ATTENUATION OF LOCOMOTOR RECOVERY AFTER SPINAL CORD INJURY

    PubMed Central

    Hook, Michelle A.; Washburn, Stephanie N.; Moreno, Georgina; Woller, Sarah A.; Puga, Denise; Lee, Kuan H.; Grau, James W.

    2010-01-01

    Morphine is one of the most commonly prescribed medications for the treatment of chronic pain after a spinal cord injury (SCI). Despite widespread use, however, little is known about the secondary consequences of morphine use after SCI. Unfortunately, our previous studies show that administration of a single dose of morphine, in the acute phase of a moderate spinal contusion injury, significantly attenuates locomotor function, reduces weight gain, and produces symptoms of paradoxical pain (Hook et al., 2009). The current study focused on the cellular mechanisms that mediate these effects. Based on data from other models, we hypothesized that pro-inflammatory cytokines might play a role in the morphine-induced attenuation of function. Experiment 1 confirmed that systemic morphine (20 mg/kg) administered one day after a contusion injury significantly increased expression levels of spinal IL-1β 24 hrs later. Experiment 2 extended these findings, demonstrating that a single dose of morphine (90 µg, i.t.) applied directly onto the spinal cord increased expression levels of spinal IL-1β at both 30 min and 24 hrs after administration. Experiment 3 showed that administration of an interleukin-1 receptor antagonist (IL-1ra, i.t.) prior to intrathecal morphine (90 µg), blocked the adverse effects of morphine on locomotor recovery. Further, pre-treatment with 3 µg IL-1ra prevented the increased expression of at-level neuropathic pain symptoms that was observed 28 days later in the group treated with morphine-alone. However, the IL-1ra also had adverse effects that were independent of morphine. Treatment with the IL-1ra alone undermined recovery of locomotor function, potentiated weight loss and significantly increased tissue loss at the injury site. Overall, these data suggest that morphine disrupts a critical balance in concentrations of pro-inflammatory cytokines in the spinal cord, and this undermines recovery of function. PMID:20974246

  8. The analgesic and toxic effects of nornicotine enantiomers alone and in interaction with morphine in rodent models of acute and persistent pain

    PubMed Central

    Holtman, Joseph R.; Crooks, Peter A.; Johnson-Hardy, Jaime K.; Wala, Elzbieta P.

    2009-01-01

    Neuronal nicotinic acetylcholinic receptors (nAChR) are promising targets for the development of novel analgesics. Nicotine and other nAChR-agonists produce profound analgesia in rodent models of acute and persistent pain. However, significant side-effects are of concern. Nornicotine (N-desmethyl-nicotine) appears to activate different nAChR subtypes, has a better pharmacokinetic profile, and produces less toxicity than nicotine. Little is known about its analgesic properties. In the present study, the S(−)- and R(+)- enantiomers of nornicotine were characterized with regard to analgesia and side-effects profile. Efficacy was demonstrated in rat models of pain where central sensitization is involved: i.e. the chronic constriction nerve injury model of peripheral neuropathy and the formalin model of tonic inflammatory pain. The desirable (analgesic) properties resided predominantly in the S(−)- rather than the R(+)- enantiomer. In contrast, undesirable effects (motor in-coordination, reduced locomotor activity, ataxia) were more pronounced with the R(+)- enantiomer. This is an interesting finding, which may suggest separation of toxicity from analgesia by utilization of S(−)-enantiomer of nornicotine. Maximum analgesic effectiveness without significant side-effects was achieved when S(−)-nornicotine (sub-analgesic dose) was combined with a low-dose of the μ-opioid, morphine. These preclinical data suggest that S(−)-nornicotine may be of value, either alone or in combination with an opioid, for treatment of a broad-spectrum of pain (i.e. nociceptive, neuropathic, mixed pain). PMID:19800911

  9. Assessment of Intraoperative Intra-articular Morphine and Clonidine Injection in the Acute Postoperative Period After Hip Arthroscopy

    PubMed Central

    Cogan, Charles J.; Knesek, Michael; Tjong, Vehniah K.; Nair, Rueben; Kahlenberg, Cynthia; Dunne, Kevin F.; Kendall, Mark C.; Terry, Michael A.

    2016-01-01

    Background: Previous authors have suggested that intra-articular morphine and clonidine injections after knee arthroscopy have demonstrated equivocal analgesic effect in comparison with bupivacaine while circumventing the issue of chondrotoxicity. There have been no studies evaluating the effect of intra-articular morphine after hip arthroscopy. Purpose: To evaluate the efficacy of intra-articular morphine in combination with clonidine on postoperative pain and narcotic consumption after hip arthroscopy surgery for femoroacetabular impingement. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective chart review was performed on 43 patients that underwent hip arthroscopy for femoroacetabular impingement at a single institution between September 2014 and May 2015. All patients received preoperative celecoxib and acetaminophen, and 22 patients received an additional intra-articular injection of 10 mg morphine and 100 μg of clonidine at the conclusion of the procedure. Narcotic consumption, duration of anesthesia recovery, and perioperative pain scores were compared between the 2 groups. Results: Patients who received intra-articular morphine and clonidine used significantly less opioid analgesic (mEq) in the postanesthesia recovery (median difference, 17 mEq [95% CI, –32 to –2 mEq]; P = .02) compared with the control group. There were no differences in time spent in recovery before hospital discharge or in visual analog pain scores recorded immediately postoperatively and at 1 hour after surgery. Conclusion: Intraoperative intra-articular injection of morphine and clonidine significantly reduced the narcotic requirement during the postsurgical recovery period after hip arthroscopy. The reduction in postsurgical opioids may decrease adverse effects, improve overall pain management, and lead to better quality of recovery and improved patient satisfaction. PMID:26977421

  10. [Surgical treatment of acute mediastinitis].

    PubMed

    Krüger, M; Decker, S; Schneider, J P; Haverich, A; Schega, O

    2016-06-01

    Despite modern intensive care management, acute mediastinitis is still associated with a high morbidity and mortality (up to approximately 40 %). Effective antibiotic therapy, intensive care management, elimination of the causative sources of infection and drainage of the affected mediastinal compartments are the cornerstones of therapy in a multidisciplinary treatment concept. Early diagnosis, prompt and uncompromising initial therapy and planned computed tomography (CT) control after the first stages of therapy in order to decide on the necessity for surgical re-interventions are essential for achieving optimal results. Knowledge of the specific anatomical characteristics is crucial for the understanding of this disease and its treatment; therefore, the current knowledge on fascial layers and interstitial spaces from the neck to the mediastinum is described and discussed. A possible foudroyant spread of the infection, especially within the posterior mediastinum, has to be anticipated. The approach to the mediastinum depends on the mediastinal compartments affected, on the causative disease and on the patient's clinical situation. The surgical approach should be adapted to the particular clinical situation of the individual patient and to the surgical experience of the surgeon. When in doubt, the more invasive approach to the mediastinum, such as bilateral thoracotomy, is recommended. An ascending mediastinitis due to pancreatitis is a very rare condition; however, as chest pains are often the main clinical sign surgeons should be aware of this differential diagnosis. An intraoperative brown-black serous fluid in the mediastinal tissue is virtually pathognomonic. The treatment results of esophageal perforation as the most frequent cause of mediastinitis have been improved by integration of various interventional procedures. Hyperbaric oxygen therapy or immunoglobulin treatment can play an auxiliary role in selected patients with acute mediastinitis. PMID

  11. Effects of Brugmansia arborea Extract and Its Secondary Metabolites on Morphine Tolerance and Dependence in Mice.

    PubMed

    Mattioli, Laura; Bracci, Antonio; Titomanlio, Federica; Perfumi, Marina; De Feo, Vincenzo

    2012-01-01

    The aim of the present study was to investigate, in vivo, the effect of a Brugmansia arborea extract (BRU), chromatographic fractions (FA and FNA), and isolated alkaloids on the expression and the acquisition of morphine tolerance and dependence. Substances were acutely (for expression) or repeatedly (for acquisition) administered in mice treated with morphine twice daily for 5 or 6 days, in order to make them tolerant or dependent. Morphine tolerance was assessed using the tail-flick test at 1st and 5th days. Morphine dependence was evaluated through the manifestation of withdrawal symptoms induced by naloxone injection at 6th day. Results showed that BRU significantly reduced the expression of morphine tolerance, while it was ineffective to modulate its acquisition. Chromatographic fractions and pure alkaloids failed to reduce morphine tolerance. Conversely BRU, FA, and pure alkaloids administrations significantly attenuated both development and expression of morphine dependence. These data suggest that Brugmansia arborea Lagerh might have human therapeutic potential for treatment of opioid addiction. PMID:22454681

  12. Effects of Brugmansia arborea Extract and Its Secondary Metabolites on Morphine Tolerance and Dependence in Mice

    PubMed Central

    Mattioli, Laura; Bracci, Antonio; Titomanlio, Federica; Perfumi, Marina; De Feo, Vincenzo

    2012-01-01

    The aim of the present study was to investigate, in vivo, the effect of a Brugmansia arborea extract (BRU), chromatographic fractions (FA and FNA), and isolated alkaloids on the expression and the acquisition of morphine tolerance and dependence. Substances were acutely (for expression) or repeatedly (for acquisition) administered in mice treated with morphine twice daily for 5 or 6 days, in order to make them tolerant or dependent. Morphine tolerance was assessed using the tail-flick test at 1st and 5th days. Morphine dependence was evaluated through the manifestation of withdrawal symptoms induced by naloxone injection at 6th day. Results showed that BRU significantly reduced the expression of morphine tolerance, while it was ineffective to modulate its acquisition. Chromatographic fractions and pure alkaloids failed to reduce morphine tolerance. Conversely BRU, FA, and pure alkaloids administrations significantly attenuated both development and expression of morphine dependence. These data suggest that Brugmansia arborea Lagerh might have human therapeutic potential for treatment of opioid addiction. PMID:22454681

  13. Effects of a Rhodiola rosea L. extract on acquisition and expression of morphine tolerance and dependence in mice.

    PubMed

    Mattioli, Laura; Perfumi, Marina

    2011-03-01

    This study investigated the effect of Rhodiola rosea L. extract on acquisition and expression of morphine tolerance and dependence in mice. Therefore animals were injected with repeated administration of morphine (10 mg/kg, subcutaneous) twice daily for five or six days, in order to make them tolerant or dependent. Rhodiola rosea L. extract (0, 10, 15 and 20 mg/kg) was administered by the intragastric route 60 min prior to each morphine injection (for acquisition) or prior the last injection of morphine or naloxone on test day (for tolerance or dependence expression, respectively). Morphine tolerance was evaluated by testing its analgesic effect in the tail flick test at the 1st and 5th days. Morphine dependence was evaluated by counting the number of withdrawal signs (jumping, rearing, forepaw tremor, teeth chatter) after naloxone injection (5 mg/kg; intraperitoneal) on the test day (day 6). Results showed that Rhodiola rosea L. extract significantly reduced the expression of morphine tolerance, while it was ineffective in modulating its acquisition. Conversely, Rhodiola rosea L. extract significantly and dose-dependently attenuated both development and expression of morphine dependence after chronic or acute administration. These data suggest that Rhodiola rosea L. may have human therapeutic potential for treatment of opioid addiction. PMID:20142299

  14. Morphine treatment selectively regulates expression of rat pituitary POMC and the prohormone convertases PC1/3 and PC2

    PubMed Central

    Anghel, Adrian; Paez Espinosa, Enma V.; Stuart, Ronald C.; Lutfy, Kabirullah; Nillni, Eduardo A.; Friedman, Theodore C.

    2013-01-01

    The prohormone convertases, PC1/3 and PC2 are thought to be responsible for the activation of many prohormones through processing including the endogenous opioid peptides. We propose that maintenance of hormonal homeostasis can be achieved, in part, via alterations in levels of these enzymes that control the ratio of active hormone to prohormone. In order to test the hypothesis that exogenous opioids regulate the endogenous opioid system and the enzymes responsible for their biosynthesis, we studied the effect of short-term morphine or naltrexone treatment on pituitary PC1/3 and PC2 as well as on the level of pro-opiomelanocortin (POMC), the precursor gene for the biosynthesis of the endogenous opioid peptide, beta-endorphin. Using ribonuclease protection assays, we observed that morphine down-regulated and naltrexone up-regulated rat pituitary PC1/3 and PC2 mRNA. Immunofluorescence and Western blot analysis confirmed that the protein levels changed in parallel with the changes in mRNA levels and were accompanied by changes in the levels of phosphorylated cyclic-AMP response element binding protein. We propose that the alterations of the prohormone processing system may be a compensatory mechanism in response to an exogenous opioid ligand whereby the organism tries to restore its homeostatic hormonal milieu following exposure to the opioid, possibly by regulating the levels of multiple endogenous opioid peptides and other neuropeptides in concert. PMID:23891651

  15. [Improvement of treatment results of acute cholecystitis].

    PubMed

    Sovtsov, S A; Prilepina, E V

    2015-01-01

    The aim of this study was investigation of treatment results of acute cholecystitis according to suggested forms of cholecystitis by international experts in the research (Tokyo-2007). It was analyzed the immediate treatment results of 1399 patients with acute cholecystitis for the last 4 years in the Chelyabinsk Regional Hospital No3. 912 patients had acute cholecystitis I degree (easy cholecystitis), 270 patients--II (moderate) degree and 217 patients--III degree (severe cholecystitis). It was operated 1281 patients. Operating activity was 91.5%. Postoperative mortality in whole patients group was 0.78%. The authors suggested the main principles such as early, differentiated by the volume operative interventions according to graduations of investigation "Tokyo-2007". Controlled trial of treatment results of patients randomized on three degrees of acute cholecystitis observed appropriateness of allocation of these groups. It is necessary for differentiated treatment and improvement of treatment results of patients with acute cholecystitis. PMID:26031820

  16. Inhibitory effect of spinal mGlu(5) receptor antisense oligonucleotide on the up-regulated expression of spinal G protein associated with chronic morphine treatment.

    PubMed

    Chen, Moxi; Zhang, Xiaoli; Xu, Hao; Ma, Xiaqing; Jiang, Wei; Xu, Tao

    2014-01-15

    Knockdown of spinal metabotropic glutamate 5 (mGlu5) receptor was shown to inhibit the development of intrathecal morphine antinociceptive tolerance. The present work was designed to evaluate the expression of spinal G-protein during morphine tolerance and knockdown of spinal mGlu5 receptor with antisense oligonucleotide (ODN). Rats were treated with saline, morphine, mGlu5 receptor antisense or mismatch ODN intrathecally. Behavioral tests were employed to test the thermal and mechanical pain thresholds. Five days later, rats were scarified and spinal expression of spinal Gαi, Gαo, Gαq and Gβ were detected. Consistent with the previous results, knockdown of spinal mGlu5 receptor could inhibit spinal morphine antinociceptive tolerance in behavioral tests (P<0.05). The mGlu5 receptor antisense ODN produced a significant reduction in mGlu5 receptor protein of about 56.6% compared with the control group (P<0.05). Expression of spinal Gαi, Gαo, Gαq and Gβ were up-regulated while morphine tolerance developed (P<0.05). Antisense ODN of spinal mGlu5 receptor, but not mismatched ODN, reduced the spinal dorsal horn levels of Gαi, Gαo, Gαs, Gαq and Gβ (P<0.05). We conclude that expression of spinal G (αi, αo, αs, αq and β) protein may be up-regulated after chronic morphine treatment which could be attenuated by knockdown of spinal mGlu5 receptor with antisense ODN. PMID:24296320

  17. [Thrombolytic treatment of acute stroke].

    PubMed

    Amiri, H; Hacke, W; Bösel, J

    2011-11-01

    Ischemic stroke is a medical emergency and must be treated as quickly as possible according to the "time-is-brain" concept. At present, intravenous administration of recombinant tissue plasminogen activator (rt-PA) within the first 4.5 h from stroke onset is the only effective treatment but is currently still only approved within the first 3 h from onset of symptoms (0.9 mg/kg body weight, maximum dose 90 mg, 10% of the cumulative dose as bolus, remaining 90% subsequently infused within 60 min). The therapeutic effect of magnetic resonance imaging (MRI) based thrombolytic therapy beyond the 4.5 h time window remains to be proven. Proximal occlusions of the middle cerebral artery can be treated successfully within the first 6 h from stroke onset by catheter-based intra-arterial administration of plasminogen activator leading to a significant improvement of outcome. Acute basilar artery occlusion should be treated in specialized centres using intra-arterial application of urokinase, rt-PA or mechanical recanalization but intravenous thrombolysis beyond the 3 h window is an acceptable alternative. PMID:21922224

  18. Day-to-day variations during clinical drug monitoring of morphine, morphine-3-glucuronide and morphine-6-glucuronide serum concentrations in cancer patients. A prospective observational study

    PubMed Central

    Klepstad, Pål; Hilton, Priscilla; Moen, Jorunn; Kaasa, Stein; Borchgrevink, Petter C; Zahlsen, Kolbjørn; Dale, Ola

    2004-01-01

    Background The feasibility of drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. One important factor relevant to drug monitoring is to what extent morphine, M6G and M3G serum concentrations fluctuate during stable morphine treatment. Methods We included twenty-nine patients admitted to a palliative care unit receiving oral morphine (n = 19) or continuous subcutaneous (sc) morphine infusions (n = 10). Serum concentrations of morphine, M6G and M3G were obtained at the same time on four consecutive days. If readmitted, the patients were followed for another trial period. Day-to-day variations in serum concentrations and ratios were determined by estimating the percent coefficient of variation (CV = (mean/SD) ×100). Results The patients' median morphine doses were 90 (range; 20–1460) mg/24 h and 135 (range; 30–440) mg/24 h during oral and sc administration, respectively. Intraindividual fluctuations of serum concentrations estimated by median coefficients of day-to-day variation were in the oral group for morphine 46%, for M6G 25% and for M3G 18%. The median coefficients of variation were lower in patients receiving continuous sc morphine infusions (morphine 10%, M6G 13%, M3G 9%). Conclusion These findings indicate that serum concentrations of morphine and morphine metabolites fluctuate. The fluctuations found in our study are not explained by changes in morphine doses, administration of other drugs or by time for collection of blood samples. As expected the day-to-day variation was lower in patients receiving continuous sc morphine infusions compared with patients receiving oral morphine. PMID:15461818

  19. Absorption of morphine from a slow-release emulsion used to induce morphine dependence in rats.

    PubMed

    Salem, A; Hope, W

    1998-10-01

    This study was performed to measure absorption of morphine from the injection site following treatment of rats with slow-release emulsions formulated with morphine hydrochloride and morphine base. Samples of emulsion were collected from the injection site of halothane anesthetized animals at 24 and 48 h following emulsion treatment and concentrations of morphine remaining in the emulsion were analyzed using high-performance liquid chromatography (HPLC). In another group of morphine-treated rats, at times equivalent to collecting samples of emulsion, the intensity of naloxone-precipitated withdrawal behaviors was monitored. Both morphine base- and hydrochloride-containing emulsions induced a high degree of physical dependence in animals treated over 48 h. Release of morphine from emulsions containing morphine base was slower than that from the hydrochloride formulations. In the 24-h morphine base-treated animals, approximately 45% was absorbed from the injection site as opposed to 99% in the 24-h morphine hydrochloride-treated animals. These results suggest that morphine base containing emulsions provide a more sustained exposure to the opioid. PMID:10334632

  20. Morphine Liposomal--SkyePharma: C 0401, D 0401, morphine--DepoFoam, SKY 0401.

    PubMed

    2003-01-01

    The SkyePharma PLC subsidiary SkyePharma Inc. (formerly DepoTech) is developing a sustained-release formulation of morphine sulphate [DepoMorphine, C 0401, D 0401, SKY 0401] using its DepoFoam proprietary drug delivery technology. It is intended for epidural administration in the treatment of acute postoperative pain. DepoFoam consists of microscopic spherical particles with internal aqueous chambers separated by lipid membranes containing the encapsulated drug. DepoFoam particles are synthetic replicas of natural lipids that are biodegradable and biocompatible. DepoFoam can be administered subcutaneously, intramuscularly and intrathecally. In December 2002, SkyePharma and Endo Pharmaceuticals signed a development and commercialisation agreement providing Endo Pharmaceuticals with exclusive marketing and distribution rights in the US and Canada for Depomorphine and another product, Propofol IDD-D trade mark, with options for other development products. Under the terms of the agreement, SkyePharma will receive an upfront payment and may receive further milestone payments. Skye-Pharma will also receive a share of each product's sales revenue. SkyePharma is responsible for clinical development towards the US FDA approval and for product manufacture and associated costs. Following the approval, SkyePharma will as act as a supplier, while Endo will market each product in the US and Canada. SkyePharma has received 30 million US dollars from Paul Capital Partners, a US private equity group, to develop DepoMorphine. This capital will enable SkyePharma to fund phase III clinical trials without raising extra funds. Paul Capital will have rights to 15% of any revenues from DepoMorphine until 2014, and also receive some royalties on three other SkyePharma products. However, if DepoMorphine fails in clinical trials or is declined for registration, Paul Capital will not be compensated for the investment. SkyePharma expect to conclude a European license by the end of 2003, and

  1. Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury

    PubMed Central

    Moreno, Georgina; Woller, Sarah; Puga, Denise; Hoy, Kevin; Balden, Robyn; Grau, James W.

    2009-01-01

    Abstract Prior work has shown that a high dose (20 mg/kg) of systemic morphine, required to produce significant analgesia in the acute phase of a contusion injury, undermines the long-term health of treated subjects and increases lesion size. Moreover, a single dose of systemic morphine in the early stage of injury (24 h post-injury) led to symptoms of neuropathic pain 3 weeks later, in the chronic phase. The present study examines the locus of the effects using intrathecal morphine administration. Subjects were treated with one of three doses (0, 30, or 90 μg) of intrathecal morphine 24 h after a moderate contusion injury. The 90-μg dose produced significant analgesia when subjects were exposed to noxious stimuli (thermal and incremented shock) below the level of injury. Yet, despite analgesic efficacy, intrathecal morphine significantly attenuated the recovery of locomotor function and increased lesion size rostral to the injury site. A single dose of 30 or 90 μg of intrathecal morphine also decreased weight gain, and more than doubled the incidence of mortality and autophagia when compared to vehicle-treated controls. Morphine is one of the most effective pharmacological agents for the treatment of neuropathic pain and, therefore, is indispensable for the spinally injured. Treatment can, however, adversely affect the recovery process. A morphine-induced attenuation of recovery may result from increases in immune cell activation and, subsequently, pro-inflammatory cytokine concentrations in the contused spinal cord. PMID:19388818

  2. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  3. Treatment Options for Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  4. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  5. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  6. Open Treatment of Acute Scapholunate Instability.

    PubMed

    Swanstrom, Morgan M; Lee, Steve K

    2015-08-01

    Acute treatment of scapholunate instability is important to prevent future complications of dorsal intercalated segment instability and scapholunate advanced collapse. An understanding of the fundamental normal and abnormal mechanics of this problem is vital. Diagnosis in the acute phase is based on clinical and radiographic findings and treatment focuses on primary scapholunate interosseous ligament repair with a reinforcing dorsal capsulodesis. Suture anchor repair with a modified "double-dorsal" capsulodesis is described. Current data show that open repair is a viable option in the acute setting with most patients demonstrating good to excellent functional, clinical, and radiographic results. PMID:26205704

  7. The combination of mitragynine and morphine prevents the development of morphine tolerance in mice.

    PubMed

    Fakurazi, Sharida; Rahman, Shamima Abdul; Hidayat, Mohamad Taufik; Ithnin, Hairuszah; Moklas, Mohamad Aris Mohd; Arulselvan, Palanisamy

    2013-01-01

    Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine. PMID:23292329

  8. Treatment of acute lower limb ischaemia.

    PubMed

    Lukasiewicz, Aleksander

    2016-05-01

    Acute lower limb ischaemia poses a major threat to limb survival. For many years surgical thromboembolectomy was the mainstay of treatment. Recent years have brought an endovascular revolution in the management of acute lower limb ischaemia. A wide range of endovascular procedures can nowadays be employed, providing results at least as good as the traditional surgical approach. This paper is an overview of currently utilised endovascular options as well as recent modifications of standard surgical techniques. PMID:27129066

  9. Evolving Treatments for Acute Ischemic Stroke.

    PubMed

    Zerna, Charlotte; Hegedus, Janka; Hill, Michael D

    2016-04-29

    The purpose of this article is to review advances in stroke treatment in the hyperacute period. With recent evolutions of technology in the fields of imaging, thrombectomy devices, and emergency room workflow management, as well as improvement in statistical methods and study design, there have been ground breaking changes in the treatment of acute ischemic stroke. We describe how stroke presents as a clinical syndrome and how imaging as the most important biomarker will help differentiate between stroke subtypes and treatment eligibility. The evolution of hyperacute treatment has led to the current standard of care: intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation. All patients with acute ischemic stroke are in need of hyperacute secondary prevention because the risk of recurrence is highest closest to the index event. The dominant themes of modern stroke care are the use of neurovascular imaging and speed of diagnosis and treatment. PMID:27126651

  10. Acute effects of morphine and opioid peptides on the motility and responses of rat colon to electrical stimulation.

    PubMed Central

    Gillan, M. G.; Pollock, D.

    1980-01-01

    1 Morphine and leucine- and methionine-enkephalins inhibited the contractile response of the pithed rat colon to electrical stimulation of the spinal motor outflows and inhibited motor responses of the isolated colon to field stimulation. 2 Morphine and the opioid peptides also had an excitatory action in the colon. In the pithed rat, opiates caused regular fluctuations in intracolonic pressure and in the isolated colon, caused regular waves of contraction. This excitatory response was produced by low concentrations of the enkephalins (2 X 10(-8) M, 2 X 10(-9) M), was stereospecific and was antagonized by naloxone. 3 Opiate-induced contractions in the isolated colon were inhibited by catecholamines, adenine nucleotides and by phosphodiesterase inhibitors. These contractions were unaffected by ergotamine and tolazoline, or by propranolol. 4 The excitatory action of opiates in the isolated colon was not antagonized and usually was potentiated by atropine, (+)-tubocurarine and hexamethonium. In the absence of opiates, these drugs also produced similar waves of contraction, which were unaffected by naloxone. 5 Opiate-induced contractions occurred in colon rendered unresponsive to 5-hydroxytryptamine (5-HT) and these contractions were potentiated by the 5-HT antagonist, lysergic acid diethylamide, which, when administered alone, caused similar contractions. The 5-HT antagonist, cyproheptadine, inhibited opiate-induced contractions but was non-specific, since it also inhibited responses of the colon to carbachol and KC1. 6 Opiate-induced contractions were unaffected by procaine and were potentiated by tetrodotoxin. Both of these drugs, when administered alone, produced waves of contractions, which were similar to those produced by opiates but were unaffected by naloxone. 7 Contractions produced in the isolated colon either by opiates, atropine or (+)-tubocurarine, or any combination of these drugs, were inhibited by field stimulation applied at the peak of a wave of

  11. Long-term morphine treatment enhances proteasome-dependent degradation of G beta in human neuroblastoma SH-SY5Y cells: correlation with onset of adenylate cyclase sensitization.

    PubMed

    Moulédous, Lionel; Neasta, Jérémie; Uttenweiler-Joseph, Sandrine; Stella, Alexandre; Matondo, Mariette; Corbani, Maïthé; Monsarrat, Bernard; Meunier, Jean-Claude

    2005-08-01

    The initial aim of this study was to identify protein changes associated with long-term morphine treatment in a recombinant human neuroblastoma SH-SY5Y clone (sc2) stably overexpressing the human mu-opioid (MOP) receptor. In MOP receptor-overexpressing sc2 cells, short-term morphine exposure was found to be much more potent and efficacious in inhibiting forskolin-elicited production of cAMP, and long-term morphine exposure was shown to induce a substantially higher degree of opiate dependence, as reflected by adenylate cyclase sensitization, than it did in wild-type neuroblastoma cells. Differential proteomic analysis of detergent-resistant membrane rafts isolated from untreated and chronically morphine-treated sc2 cells revealed long-term morphine exposure to have reliably induced a 30 to 40% decrease in the abundance of five proteins, subsequently identified by mass spectrometry as G protein subunits alphai(2), alphai(3), beta(1), and beta(2), and prohibitin. Quantitative Western blot analyses of whole-cell extracts showed that long-term morphine treatment-induced down-regulation of Gbeta but not of the other proteins is highly correlated (r(2) = 0.96) with sensitization of adenylate cyclase. Down-regulation of Gbeta and adenylate cyclase sensitization elicited by long-term morphine treatment were suppressed in the presence of carbobenzoxy-l-leucyl-l-leucyl-l-norvalinal (MG-115) or lactacystin. Thus, sustained activation of the MOP receptor by morphine in sc2 cells seems to promote proteasomal degradation of Gbeta to sensitize adenylate cyclase. Together, our data suggest that the long-term administration of opiates may elicit dependence by altering the neuronal balance of heterotrimeric G proteins and adenylate cyclases, with the ubiquitin-proteasome pathway playing a pivotal role. PMID:15901846

  12. Morphine-theophylline interaction: antagonism or facilitation?

    PubMed Central

    Brailowsky, S.; Guerrero-Muñoz, F.; Luján, M.; Shkurovich, M.

    1981-01-01

    1 Morphine-theophylline interactions were investigated in both acute and narcotic-dependent preparations, in vitro and in vivo, using four different experimental models: LD50 doses of morphine and naloxone in the mouse; naloxone-induced contractions in the electrically-stimulated and opiate-dependent isolated ileum of the guinea-pig; naloxone-induced jumps in the mouse; an calcium uptake in synaptosomal preparations. 2 The LD50 of morphine was significantly increased by theophylline. 3 The lethal effect of theophylline was potentiated by pretreatment of the animals with naloxone. 4 Theophylline displayed protective effects in the inhibitory response to morphine and antagonism to the withdrawal response induced by naloxone in the electrically-stimulated isolated ileum of the guinea-pig. 5 The number of jumps induced by naloxone in morphine-dependent mice was significantly diminished by theophylline. 6 The inhibitory effect of morphine on the synaptosomal uptake of calcium was decreased by theophylline. 7 The effects of both morphine and theophylline on the cyclic nucleotides and the possible role of calcium in these actions are discussed. PMID:7272590

  13. [SURGICAL TREATMENT OF AN ACUTE MESENTERIAL ISCHEMIA].

    PubMed

    Shepehtko, E N; Garmash, D A; Kurbanov, A K; Marchenko, V O; Kozak, Yu S

    2016-04-01

    Experience of surgical treatment of 143 patients, suffering an acute mesenterial ischemia, was summarized. Isolated intestinal resection was performed in 41 patients (lethality 65.9%), intestinal resection with the mesenterial vessels thrombembolectomy--in 9 (lethality 33.3%). After performance of the combined intervention postoperative lethality was in two times lower, than after isolated intestinal resection. PMID:27434952

  14. Radioimmunotherapy for Treatment of Acute Leukemia.

    PubMed

    Bodet-Milin, Caroline; Kraeber-Bodéré, Françoise; Eugène, Thomas; Guérard, François; Gaschet, Joëlle; Bailly, Clément; Mougin, Marie; Bourgeois, Mickaël; Faivre-Chauvet, Alain; Chérel, Michel; Chevallier, Patrice

    2016-03-01

    Acute leukemias are characterized by accumulation of immature cells (blasts) and reduced production of healthy hematopoietic elements. According to the lineage origin, two major leukemias can be distinguished: acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Although the survival rate for pediatric ALL is close to 90%, half of the young adults with AML or ALL and approximately 90% of older patients with AML or ALL still die of their disease, raising the need for innovative therapeutic approaches. As almost all leukemic blasts express specific surface antigens, targeted immunotherapy appears to be particularly promising. However, published results of immunotherapy alone are generally modest. Radioimmunotherapy (RIT) brings additional therapeutic mechanisms using radiolabeled monoclonal antibodies (mAbs) directed to tumor antigens, thus adding radiobiological cytotoxicity to immunologic cytotoxicity. Because of the high radiosensitivity of tumor cells and the diffuse widespread nature of the disease, making it rapidly accessible to circulating radiolabeled mAbs, acute leukemias represent relevant indications for RIT. With the development of recombinant and humanized mAbs, innovative radionuclides, and more efficient radiolabeling and pretargeting techniques, RIT has significantly improved over the last 10 years. Different approaches of α and β RIT targeting CD22, CD33, CD45, or CD66 antigens have already been evaluated or are currently being developed in the treatment of acute leukemia. This review summarizes the preclinical and clinical studies demonstrating the potential of RIT in treatment of AML and ALL. PMID:26897718

  15. Corticosteroids in the treatment of acute asthma

    PubMed Central

    Alangari, Abdullah A.

    2014-01-01

    Asthma is a prevalent chronic disease of the respiratory system and acute asthma exacerbations are among the most common causes of presentation to the emergency department (ED) and admission to hospital particularly in children. Bronchial airways inflammation is the most prominent pathological feature of asthma. Inhaled corticosteroids (ICS), through their anti-inflammatory effects have been the mainstay of treatment of asthma for many years. Systemic and ICS are also used in the treatment of acute asthma exacerbations. Several international asthma management guidelines recommend the use of systemic corticosteroids in the management of moderate to severe acute asthma early upon presentation to the ED. On the other hand, ICS use in the management acute asthma has been studied in different contexts with encouraging results in some and negative in others. This review sheds some light on the role of systemic and ICS in the management of acute asthma and discusses the current evidence behind their different ways of application particularly in relation to new developments in the field. PMID:25276236

  16. The role of morphine glucuronides in cancer pain.

    PubMed

    Mercadante, S

    1999-03-01

    Morphine metabolites are involved in various ways in determining the complex effects of morphine, both favourable and adverse, and may complicate the clinical use of morphine in the treatment of cancer pain. The production and effects of the principal morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, in both normal and pathological states have been reviewed in the current literature. Therapeutic implications are also reviewed on the basis of experimental and clinical reports. The presence of these metabolites should be recognized in the chronic treatment of cancer pain with morphine, especially in the presence of renal impairment, and should be considered to have an important influence on opioid responsiveness, defined as a balance between the achievement of an optimal analgesia and the occurrence of adverse effects. PMID:10474692

  17. Delay of Morphine Tolerance by Palmitoylethanolamide

    PubMed Central

    Di Cesare Mannelli, Lorenzo; Corti, Francesca; Micheli, Laura; Zanardelli, Matteo; Ghelardini, Carla

    2015-01-01

    In spite of the potency and efficacy of morphine, its clinical application for chronic persistent pain is limited by the development of tolerance to the antinociceptive effect. The cellular and molecular mechanisms underlying morphine tolerance are complex and still unclear. Recently, the activation of glial cells and the release of glia-derived proinflammatory mediators have been suggested to play a role in the phenomenon. N-Palmitoylethanolamine (PEA) is an endogenous compound with antinociceptive effects able to reduce the glial activation. On this basis, 30 mg kg−1 PEA was subcutaneously daily administered in morphine treated rats (10 mg kg−1 intraperitoneally, daily). PEA treatment significantly attenuated the development of tolerance doubling the number of days of morphine antinociceptive efficacy in comparison to the vehicle + morphine group. PEA prevented both microglia and astrocyte cell number increase induced by morphine in the dorsal horn; on the contrary, the morphine-dependent increase of spinal TNF-α levels was not modified by PEA. Nevertheless, the immunohistochemical analysis revealed significantly higher TNF-α immunoreactivity in astrocytes of PEA-protected rats suggesting a PEA-mediated decrease of cytokine release from astrocyte. PEA intervenes in the nervous alterations that lead to the lack of morphine antinociceptive effects; a possible application of this endogenous compound in opioid-based therapies is suggested. PMID:25874232

  18. Effects of high-dose selegiline on morphine reinforcement and precipitated withdrawal in dependent rats.

    PubMed

    Grasing, K; He, S

    2005-02-01

    Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with psychostimulant and neuroprotective effects. Several lines of evidence suggest that treatment with selegiline at doses that exceed levels required for inhibition of MAO can produce distinct pharmacologic effects. The purpose of this study was to evaluate the effects of chronic treatment with high-dose selegiline on extinction responding, cue-induced reinstatement, morphine reinforcement and naloxone-precipitated withdrawal. After pretreatment with noncontingent morphine to establish opiate dependence, rats acquired self-administration of 3.2 mg/kg per injection of morphine under a progressive ratio schedule. Daily treatment with saline or 6.4 mg/kg per day of selegiline was then administered over extinction, reinstatement and re-acquisition of morphine self-administration. To enhance or diminish the potential for psychostimulant effects, selegiline was administered either immediately prior to (pre-session) or 1 h following (post-session) extinction, reinstatement and self-administration sessions. Pre-session selegiline decreased the number of ratios completed on days 2, 3 and 4 of extinction, and decreased morphine self-administration during all four re-acquisition sessions. When administered at the same dose level, post-session selegiline decreased responding on the fourth extinction session, and was ineffective in modifying re-acquisition of self-administration. Selegiline administered by either schedule did not modify cue-induced reinstatement. Daily treatment with 6.4 mg/kg per day of selegiline did not modify self-administration of food under a progressive ratio schedule. Acute treatment with single, 6.4 mg/kg doses of selegiline attenuated naloxone-induced increases in ptosis and global withdrawal score, but did not modify any other sign of withdrawal or global withdrawal score calculated without ratings of ptosis. In conclusion, high-dose selegiline can attenuate extinction responding

  19. Morphine: Myths and Reality

    MedlinePlus

    ... and Families Take the Quiz Morphine: Myths and Reality February, 2013 The mere mention of “Morphine” can ... due to misinformation and lack of training. The reality is that Morphine (and other opiates that work ...

  20. Acute withdrawal: diagnosis and treatment.

    PubMed

    Brust, John C M

    2014-01-01

    Symptoms of alcohol withdrawal range in severity from mild "hangover" to fatal delirium tremens (DTs). Tremor, hallucinosis, and seizures usually occur within 48 hours of abstinence. Seizures tend to be generalized without focality, occurring singly or in a brief cluster, but status epilepticus is not unusual. DTs usually appears after 48 hours of abstinence and consists of marked inattentiveness, agitation, hallucinations, fluctuating level of alertness, marked tremulousness, and sympathetic overactivity. The mainstay of treatment for alcohol withdrawal is benzodiazepine pharmacotherapy, which can be used to control mild early symptoms, to prevent progression to DTs, or to treat DTs itself. Alternative less evidence-based pharmacotherapies include phenobarbital, anticonvulsants, baclofen, gamma-hydroxybutyric acid, beta-blockers, alpha-2-agonists, and N-methyl-d-aspartate receptor blockers. Treatment of DTs is a medical emergency requiring heavy sedation in an intensive care unit, with close attention to autonomic instability, fever, fluid loss, and electrolyte imbalance. Frequent comorbid disorders include hypoglycemia, liver failure, pancreatitis, sepsis, meningitis, intracranial hemorrhage, and Wernicke-Korsakoff syndrome. PMID:25307572

  1. Analgesia or Addiction?: Implications for Morphine Use after Spinal Cord Injury

    PubMed Central

    Moreno, Georgina L.; Hart, Nigel; Wellman, Paul J.; Grau, James W.; Hook, Michelle A.

    2012-01-01

    Abstract Opioid analgesics are among the most effective agents for treatment of moderate to severe pain. However, the use of morphine after a spinal cord injury (SCI) can potentiate the development of paradoxical pain symptoms, and continuous administration can lead to dependence, tolerance, and addiction. Although some studies suggest that the addictive potential of morphine decreases when it is used to treat neuropathic pain, this has not been studied in a SCI model. Accordingly, the present studies investigated the addictive potential of morphine in a rodent model of SCI using conditioned place preference (CPP) and intravenous self-administration paradigms. A contusion injury significantly increased the expression of a CPP relative to sham and intact controls in the acute phase of injury. However, contused animals self-administered significantly less morphine than sham and intact controls, but this was dose-dependent; at a high concentration, injured rats exhibited an increase in drug-reinforced responses over time. Exposure to a high concentration of morphine impeded weight gain and locomotor recovery. We suggest that the increased preference observed in injured rats reflects a motivational effect linked in part to the drug's anti-nociceptive effect. Further, although injured rats exhibited a suppression of opiate self-administration, when given access to a high concentration, addictive-like behavior emerged and was associated with poor recovery. PMID:22214368

  2. Morphine is an arteriolar vasodilator in man

    PubMed Central

    Afshari, Reza; Maxwell, Simon R J; Webb, David J; Bateman, D Nicholas

    2009-01-01

    AIM The mechanisms of action of morphine on the arterial system are not well understood. The aim was to report forearm vascular responses, and their mediation, to intra-arterial morphine in healthy subjects. METHODS Three separate protocols were performed: (i) dose ranging; (ii) acute tolerance; (iii) randomized crossover mechanistic study on forearm blood flow (FBF) responses to intrabrachial infusion of morphine using venous occlusion plethysmography. Morphine was infused either alone (study 1 and 2), or with an antagonist: naloxone, combined histamine-1 and histamine-2 receptor blockade or during a nitric oxide clamp. RESULTS Morphine caused an increase in FBF at doses of 30 µg min−1[3.25 (0.26) ml min−1 100 ml−1][mean (SEM)] doubling at 100 µg min−1 to 5.23 (0.53) ml min−1 100 ml−1. Acute tolerance was not seen to 50 µg min−1 morphine, with increased FBF [3.96 (0.35) ml min−1 100 ml−1] (P = 0.003), throughout the 30-min infusion period. Vasodilatation was abolished by pretreatment with antihistamines (P = 0.008) and the nitric oxide clamp (P < 0.001), but not affected by naloxone. The maximum FBF with pretreatment with combined H1/H2 blockade was 3.06 (0.48) and 2.90 (0.17) ml min−1 100 ml−1 after 30 min, whereas with morphine alone it reached 4.3 (0.89) ml min−1 100 ml−1. CONCLUSIONS Intra-arterial infusion of morphine into the forearm circulation causes vasodilatation through local histamine-modulated nitric oxide release. Opioid receptor mechanisms need further exploration. PMID:19371311

  3. What's New in Adult Acute Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Topic Additional resources for acute myeloid leukemia What’s new in acute myeloid leukemia research and treatment? Researchers ... benefit from current treatments. Researchers are studying many new chemo drugs for use in AML, including: Sapacitabine, ...

  4. Microbiology and treatment of acute apical abscesses.

    PubMed

    Siqueira, José F; Rôças, Isabela N

    2013-04-01

    Acute apical abscess is the most common form of dental abscess and is caused by infection of the root canal of the tooth. It is usually localized intraorally, but in some cases the apical abscess may spread and result in severe complications or even mortality. The reasons why dental root canal infections can become symptomatic and evolve to severe spreading and sometimes life-threatening abscesses remain elusive. Studies using culture and advanced molecular microbiology methods for microbial identification in apical abscesses have demonstrated a multispecies community conspicuously dominated by anaerobic bacteria. Species/phylotypes commonly found in these infections belong to the genera Fusobacterium, Parvimonas, Prevotella, Porphyromonas, Dialister, Streptococcus, and Treponema. Advances in DNA sequencing technologies and computational biology have substantially enhanced the knowledge of the microbiota associated with acute apical abscesses and shed some light on the etiopathogeny of this disease. Species richness and abundance and the resulting network of interactions among community members may affect the collective pathogenicity and contribute to the development of acute infections. Disease modifiers, including transient or permanent host-related factors, may also influence the development and severity of acute abscesses. This review focuses on the current evidence about the etiology and treatment of acute apical abscesses and how the process is influenced by host-related factors and proposes future directions in research, diagnosis, and therapeutic approaches to deal with this disease. PMID:23554416

  5. Microbiology and Treatment of Acute Apical Abscesses

    PubMed Central

    Rôças, Isabela N.

    2013-01-01

    SUMMARY Acute apical abscess is the most common form of dental abscess and is caused by infection of the root canal of the tooth. It is usually localized intraorally, but in some cases the apical abscess may spread and result in severe complications or even mortality. The reasons why dental root canal infections can become symptomatic and evolve to severe spreading and sometimes life-threatening abscesses remain elusive. Studies using culture and advanced molecular microbiology methods for microbial identification in apical abscesses have demonstrated a multispecies community conspicuously dominated by anaerobic bacteria. Species/phylotypes commonly found in these infections belong to the genera Fusobacterium, Parvimonas, Prevotella, Porphyromonas, Dialister, Streptococcus, and Treponema. Advances in DNA sequencing technologies and computational biology have substantially enhanced the knowledge of the microbiota associated with acute apical abscesses and shed some light on the etiopathogeny of this disease. Species richness and abundance and the resulting network of interactions among community members may affect the collective pathogenicity and contribute to the development of acute infections. Disease modifiers, including transient or permanent host-related factors, may also influence the development and severity of acute abscesses. This review focuses on the current evidence about the etiology and treatment of acute apical abscesses and how the process is influenced by host-related factors and proposes future directions in research, diagnosis, and therapeutic approaches to deal with this disease. PMID:23554416

  6. Pycnogenol treatment of acute hemorrhoidal episodes.

    PubMed

    Belcaro, Gianni; Cesarone, Maria Rosaria; Errichi, Bruno; Di Renzo, Andrea; Grossi, Maria Giovanna; Ricci, Andrea; Dugall, Mark; Cornelli, Umberto; Cacchio, Marisa; Rohdewald, Peter

    2010-03-01

    We investigated the efficacy of orally and topically applied Pycnogenol for the management of acute hemorrhoidal attacks in a controlled, randomized study with 84 subjects. Within less than 48 h of onset of an acute attack, patients were enrolled and signs and symptoms were scored. This evaluation was repeated after seven days' treatment and again seven days following treatment cessation. The decrease in scores was significantly more pronounced in the Pycnogenol-treated groups than in the control group given placebo (p < 0.05), showing the efficacy of Pycnogenol for relieving signs and symptoms of acute external hemorrhoids. In a group of patients given topical (0.5%) Pycnogenol in addition to oral Pycnogenol the improvement in symptoms set in significantly faster and was more pronounced. The most prominent symptom, hemorrhoidal bleeding, was completely absent in all patients treated with Pycnogenol for seven days and also at the 14 days follow-up. In contrast, bleedings were still observed in the control group during the two weeks follow-up. This study indicates that Pycnogenol, both in oral and in topical form, is effective for controlling this common, disabling health problem. The application of Pycnogenol eases the management of acute hemorrhoidal attacks and help avoid bleedings. PMID:20041428

  7. Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction.

    PubMed

    Thomas, Mark R; Morton, Allison C; Hossain, Rashed; Chen, Beining; Luo, Lei; Shahari, Nur Nazihah B Md; Hua, Peng; Beniston, Richard G; Judge, Heather M; Storey, Robert F

    2016-07-01

    Delays in the onset of action of prasugrel during primary percutaneous coronary intervention (PPCI) have been reported and could be related to the effects of morphine on gastric emptying and subsequent intestinal absorption. The study objective was to determine whether morphine delays the onset of action of prasugrel in patients with a prior history of ST-elevation myocardial infarction (STEMI) treated with PPCI. This was a crossover study of 11 aspirin-treated patients with prior history of STEMI treated with PPCI, for which prasugrel and morphine had been previously administered. Patients were randomised to receive either morphine (5 mg) or saline intravenously followed by 60 mg prasugrel. Blood samples were collected before randomised treatment and over 24 hours after prasugrel administration. The inhibitory effects of prasugrel on platelets were determined using the VerifyNow P2Y12 assay and light transmission aggregometry. Plasma levels of prasugrel and prasugrel active metabolite were measured. Platelet reactivity determined by VerifyNow PRU, VerifyNow % Inhibition and LTA was significantly higher at 30-120 minutes (min) when morphine had been co-administered compared to when saline had been co-administered. Morphine, compared to saline, significantly delayed adequate platelet inhibition after prasugrel administration (158 vs 68 min; p = 0.006). Patients with delayed onset of platelet inhibition also had evidence of delayed absorption of prasugrel. In conclusion, prior administration of intravenous morphine significantly delays the onset of action of prasugrel. Intravenous drugs may be necessary to reduce the risk of acute stent thrombosis in morphine-treated STEMI patients undergoing PPCI. PMID:27099137

  8. P2Y12 Receptor Antagonists and Morphine: A Dangerous Liaison?

    PubMed

    Giannopoulos, Georgios; Deftereos, Spyridon; Kolokathis, Fotios; Xanthopoulou, Ioanna; Lekakis, John; Alexopoulos, Dimitrios

    2016-09-01

    P2Y12 receptor antagonists, concurrently administered with aspirin in what has come to be commonly called dual antiplatelet therapy, are a mainstay of treatment for patients with acute coronary syndromes. Morphine, on the contrary, is a commonly used drug in the acute phase of acute coronary syndromes to relieve pain-with the added potential benefit of attenuating acutely raised sympathetic tone. In current guidelines, though, morphine is recommended with decreasing strength of recommendation. One reason is that it raises concern regarding the potentially significant interaction with antiplatelet agents, leading to impaired inhibition of platelet activation. In any case, it is still considered a mandatory part of the inventory of available medications in prehospital acute myocardial infarction management. The goal of the present review is to present published evidence on morphine and its potential interactions with P2Y12 receptor antagonists, as well as on the central issue of whether such interactions may underlie clinically significant effects on patient outcomes. PMID:27586412

  9. Fibrinogen α-chain-derived peptide is upregulated in hippocampus of rats exposed to acute morphine injection and spontaneous alternation testing

    PubMed Central

    Maki, Agatha E; Morris, Kenneth A; Catherman, Kasia; Chen, Xian; Hatcher, Nathan G; Gold, Paul E; Sweedler, Jonathan V

    2014-01-01

    Fibrinogen is a secreted glycoprotein that is synthesized in the liver, although recent in situ hybridization data support its expression in the brain. It is involved in blood clotting and is released in the brain upon injury. Here, we report changes in the extracellular levels of fibrinogen α-chain-derived peptides in the brain after injections of saline and morphine. More specifically, in order to assess hippocampus-related working memory, an approach pairing in vivo microdialysis with mass spectrometry was used to characterize extracellular peptide release from the hippocampus of rats in response to saline or morphine injection coupled with a spontaneous alternation task. Two fibrinopeptide A-related peptides derived from the fibrinogen α-chain – fibrinopeptide A (ADTGTTSEFIEAGGDIR) and a fibrinopeptide A-derived peptide (DTGTTSEFIEAGGDIR) – were shown to be consistently elevated in the hippocampal microdialysate. Fibrinopeptide A was significantly upregulated in rats exposed to morphine and spontaneous alternation testing compared with rats exposed to saline and spontaneous alternation testing (P < 0.001), morphine alone (P < 0.01), or saline alone (P < 0.01), respectively. The increase in fibrinopeptide A in rats subjected to morphine and a memory task suggests that a complex interaction between fibrinogen and morphine takes place in the hippocampus. PMID:24855564

  10. Double Dissociation of Monoacylglycerol Lipase Inhibition and CB1 Antagonism in the Central Amygdala, Basolateral Amygdala, and the Interoceptive Insular Cortex on the Affective Properties of Acute Naloxone-Precipitated Morphine Withdrawal in Rats.

    PubMed

    Wills, Kiri L; Petrie, Gavin N; Millett, Geneva; Limebeer, Cheryl L; Rock, Erin M; Niphakis, Micah J; Cravatt, Benjamin F; Parker, Linda A

    2016-06-01

    Both CB1 receptor antagonism and agonism, in particular by 2-arachidonyl glycerol (2-AG), have been shown to reduce somatic symptoms of morphine withdrawal (MWD). Here we evaluated the effects of both systemic pretreatment with the monoacylglycerol lipase (MAGL) inhibitor MJN110 (which selectively elevates 2-AG) and central administration of both MJN110 and the CB1 antagonist (AM251) on the affective properties of MWD. Acute MWD induced place aversion occurs when naloxone is administered 24 h following a single exposure to a high dose of morphine. Systemic pretreatment with the MAGL inhibitor, MJN110, prevented the aversive effects of acute MWD by a CB1 receptor-dependent mechanism. Furthermore, in a double dissociation, AM251 infusions into the central amygdala, but MJN110 infusions into the basolateral amygdala, interfered with the naloxone-precipitated MWD induced place aversion. As well, MJN110, but not AM251, infusions into the interoceptive insular cortex (a region known to be activated in acute MWD) also prevented the establishment of the place aversion by a CB1 mechanism of action. These findings reveal the respective sites of action of systemically administered MJN110 and AM251 in regulating the aversive effects of MWD. PMID:26647976

  11. Treatment of acute bronchiolitis with Chinese herbs.

    PubMed Central

    Kong, X T; Fang, H T; Jiang, G Q; Zhai, S Z; O'Connell, D L; Brewster, D R

    1993-01-01

    In a randomised single blind trial the Chinese herbs Shuang Huang Lian were evaluated for the treatment of acute bronchiolitis. Children with acute bronchiolitis and serological evidence of recent respiratory syncytial virus infection were studied in a tertiary hospital in Harbin, China. The 96 children were randomised into three treatment groups: herbs, herbs with antibiotics, and antibiotics alone. The herbs were prepared by the medical school pharmacy and administered daily by intravenous infusion for seven days. The main outcomes, assessed blindly, were symptomatic improvement in cough, fever, wheezing, chest signs, and duration of stay in hospital. The mean duration of symptoms from the start of treatment was 6.2 (confidence interval 5.6 to 6.9) days in the two groups treated with herbs compared with 8.6 (confidence interval 7.5 to 9.8) days in the group treated with antibiotics alone. The mean reductions in duration of clinical manifestations for treatment with antibiotics alone compared with herbs were: from 3.1 to 1.5 days for fever, 9.1 to 6.1 days for cough, 6.5 to 4.1 days for wheezing, and 7.2 to 4.9 days for chest crackles. No adverse effect of Shuang Huang Lian herbal treatment was detected. In conclusion, this study confirms Chinese experience with Shuang Huang Lian that it is safe and effective, and warrants further study. PMID:8503668

  12. Morphine Attenuated the Cytotoxicity Induced by Arsenic Trioxide in H9c2 Cardiomyocytes.

    PubMed

    Amini-Khoei, Hossein; Hosseini, Mir-Jamal; Momeny, Majid; Rahimi-Balaei, Maryam; Amiri, Shayan; Haj-Mirzaian, Arya; Khedri, Mostafa; Jahanabadi, Samane; Mohammadi-Asl, Ali; Mehr, Shahram Ejtemaie; Dehpour, Ahmad Reza

    2016-09-01

    Arsenic trioxide (ATO) is an efficient drug for the treatment of the patients with acute promyelocytic leukemia (APL). Inhibition of proliferation as well as apoptosis, attenuation of migration, and induction of differentiation in tumor cells are the main mechanisms through which ATO acts against APL. Despite advantages of ATO in treatment of some malignancies, certain harmful side effects, such as cardiotoxicity, have been reported. It has been well documented that morphine has antioxidant, anti-apoptotic, and cytoprotective properties and is able to attenuate cytotoxicity. Therefore, in this study, we aimed to investigate the protective effects of morphine against ATO toxicity in H9c2 myocytes using multi-parametric assay including thiazolyl blue tetrazolium bromide (MTT) assay, reactive oxygen species (ROS) generation, caspase 3 activity, nuclear factor kappa B (NF-κB) phosphorylation assay, and expression of apoptotic markers. Our results showed that morphine (1 μM) attenuated cytotoxicity induced by ATO in H9c2 cells. Results of this study suggest that morphine may have protective properties in management of cardiac toxicity in patients who receive ATO as an anti-cancer treatment. PMID:26815588

  13. Genotyping Test with Clinical Factors: Better Management of Acute Postoperative Pain?

    PubMed Central

    Hajj, Aline; Peoc’h, Katell; Laplanche, Jean-Louis; Jabbour, Hicham; Naccache, Nicole; Abou Zeid, Hicham; Yazbeck, Patricia; Rabbaa Khabbaz, Lydia

    2015-01-01

    Individualization of acute postoperative pain treatment on an evidence-based decision process is a major health concern. The aim of this study is to investigate the influence of genetic and non-genetic factors on the variability of response to morphine in acute postoperative pain. A group of nighty-five patients undergoing major surgery were included prospectively. At 24 h, a logistic regression model was carried out to determine the factors associated with morphine doses given by a Patient Controlled Analgesia device. The dose of morphine was associated with age (p = 0.011), patient weight (p = 0.025) and the duration of operation (p = 0.030). This dose decreased with patient’s age and duration of operation and increased with patient’s weight. OPRM1 and ABCB1 polymorphisms were significantly associated with administered dose of morphine (p = 0.038 and 0.012 respectively). Patients with at least one G allele for c.118A>G OPRM1 polymorphism (AG/GG) needed 4 times the dose of morphine of AA patients. Additionally, patients with ABCB1 CT and CC genotypes for c.3435C>T polymorphism were 5.6 to 7.1 times more prone to receive higher dose of morphine than TT patients. Our preliminary results support the evidence that OPRM1/ABCB1 genotypes along with age, weight and duration of operation have an impact on morphine consumption for acute postoperative pain treatment. PMID:25809606

  14. P-glycoprotein Modulates Morphine Uptake into the CNS: A Role for the Non-steroidal Anti-inflammatory Drug Diclofenac

    PubMed Central

    Sanchez-Covarrubias, Lucy; Slosky, Lauren M.; Thompson, Brandon J.; Zhang, Yifeng; Laracuente, Mei-Li; DeMarco, Kristin M.; Ronaldson, Patrick T.; Davis, Thomas P.

    2014-01-01

    Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP), induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp) that is endogenously expressed at the blood-brain barrier (BBB). The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID) that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h), as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction. PMID:24520393

  15. Changes in [3H]-UK 14304 binding to alpha 2-adrenoceptors in morphine-dependent guinea-pigs.

    PubMed Central

    Varani, K.; Beani, L.; Bianchi, C.; Borea, P. A.; Simonato, M.

    1995-01-01

    1. The aim of this study was to investigate the effect of a noradrenergic input in the cortex of morphine-dependent animals. Binding of the alpha 1-adrenoceptor ligand [3H]-prazosin did not change in cortical membranes taken from morphine-dependent as compared to control guinea-pigs. However, binding of the alpha 2-adrenoceptor ligand [3H]-UK 14304 showed decreased KD (-30%) in the absence of significant changes in Bmax, either in cortical membranes or in synaptosomes. 2. Several characteristics of this phenomenon were identified. First, it occurs in a time-dependent fashion, in that it takes 5 days of chronic morphine treatment to start developing. Second, it can be observed after acute administration of high doses of morphine (100 mg kg-1). Third, it does not require a connection with the locus coeruleus or with other subcortical structures, in that it can be reproduced in vitro in isolated cortical slices. Fourth, it requires the integrity of cortical structures, since it cannot be reproduced in vitro in cortical synaptosomes. 3. Release studies were run to attempt identification of a functional correlate of the above observations. No changes were observed in the ability of the alpha 2-adrenoceptor agonist UK 14304 to inhibit 35 mM K(+)-evoked [3H]-noradrenaline outflow from cortical synaptosomes taken from morphine-dependent as compared to control guinea-pigs. However, a large decrease in the IC50 of UK 14304 for the inhibition of 35 mM K(+)-evoked [3H]-gamma-aminobutyric acid ([3H]-GABA) outflow (41 vs. 501 nM) was observed in morphine-dependent as compared to control animals. 4. These data suggest that, in the guinea-pig, chronic morphine treatment is associated with a shift from a low to high affinity agonist state in alpha 2-adrenoceptors on cortical GABA terminals. PMID:8719786

  16. [Prophylactic measures and acute treatment of migraine].

    PubMed

    Göbel, H; Heinze, A; Heinze-Kuhn, K

    2006-11-01

    The treatment of migraine consists of the acute treatment of the migraine attack and prophylactic measures for either pharmacological or non-pharmacological management. Since the retreat of the ergotamines one can only choose between one of the well-established analgesics and one of seven triptans for the treatment of the migraine attack. Although neither a new triptan nor an innovative new application form has been introduced, the year 2006 will be remembered as the year when the first triptan (naratriptan) was released as a prescription-free over-the-counter drug and when the first sumatriptan generics were marketed in Germany. In addition to the beta-blockers metoprolol and propranolol and the calcium antagonist flunarizine two antiepileptic drugs, topiramate and valproic acid, have been rated as first-line prophylactic drugs in Germany. Due to an extensive and successful study program topiramate has been officially approved in Germany. PMID:17048020

  17. Blockade of tolerance to morphine analgesia by cocaine.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1989-07-01

    Tolerance to morphine analgesia was induced in male Sprague-Dawley rats by s.c. implantation of a morphine base pellet (75 mg) on the first and second day and determining the magnitude of tolerance 72 h after the first implant by s.c. injection of a test dose of morphine (5 mg/kg). Implantation of a cocaine hydrochloride pellet (25 mg), concurrently with morphine pellets or of a cocaine hydrochloride (50 mg) pellet after the development of tolerance, blocked both the development and expression of morphine analgesic tolerance. In morphine-pelleted animals pretreatment for 3 days with desipramine or zimelidine or phenoxybenzamine but not haloperidol produced no significant morphine tolerance. Pretreatment with a combination of desipramine and zimelidine, however, was as effective as cocaine in blocking morphine tolerance. Alpha-Methyl-p-tyrosine methyl ester counteracted the effect of cocaine in blocking morphine tolerance and potentiated the tolerance development. Blockade of morphine tolerance by cocaine was reinforced and facilitated by pretreatment with fenfluramine or p-chlorophenylalanine ethyl ester and to a lesser extent by clonidine and haloperidol. Acute administration of fenfluramine or zimelidine or a combination of desipramine and zimelidine or alpha-methyl-p-tyrosine methyl ester or p-chlorophenylalanine ethyl ester did not significantly affect morphine analgesia. The study suggests an important role of the concomitant depletion of both central noradrenaline and serotonin in the blockade of morphine tolerance by cocaine and stresses the importance of the counter-balancing functional relationship between these two neurotransmitters in the central nervous system. PMID:2780065

  18. Role of dopamine D1-like receptor within the nucleus accumbens in acute food deprivation- and drug priming-induced reinstatement of morphine seeking in rats.

    PubMed

    Sadeghzadeh, Fatemeh; Babapour, Vahab; Haghparast, Abbas

    2015-01-01

    Dopamine is a predominant neurotransmitter in the nervous system, which plays an important role in both drug priming- and cue-induced reinstatement of cocaine and heroin seeking. Therefore, in the present study, the conditioned place preference (CPP) paradigm was used to evaluate the effects of intra-accumbal administration of SCH23390 as a dopamine D1-like receptor antagonist on food deprivation (FD) and drug priming-induced reinstatement. Sixty-eight adult male albino Wistar rats weighing 200-280 g were bilaterally implanted by cannulae into the nucleus accumbens (NAc). For induction of the CPP, subcutaneous (sc) administration of morphine (5mg/kg) was used daily during a three-day conditioning phase. The conditioning score and locomotor activity were recorded by using the Ethovision software. Under extinction conditions, rats were given an 'off' period and were tested for FD-induced reinstatement following the 24-h or 48-h FD condition, and for drug priming-induced reinstatement under the sated condition following an injection of 0.5 and 1mg/kg (sc) morphine. In the next experiments, animals received different doses of intra-accumbal SCH23390 (0.25, 1 and 4 μg/0.5 μl saline) bilaterally and were subsequently tested for FD- and morphine priming-induced reinstatement. Our findings indicated that only a dose of 1mg/kg and not 0.5mg/kg of morphine induced the reinstatement of morphine. 24-h FD similar to 48-h FD induced the reinstatement of seeking behaviors facilitated by an ineffective dose of morphine (0.5mg/kg). Furthermore, the D1-like receptor antagonist attenuated FD- and drug priming-induced reinstatement dose-dependently. It is concluded that FD- and drug priming-induced reinstatement may be mediated, at least in some way, by activation of dopamine D1-like receptors in the NAc. PMID:25835321

  19. Beta blocker eye drops for treatment of acute migraine.

    PubMed

    Migliazzo, Carl V; Hagan, John C

    2014-01-01

    We report seven cases of successful treatment of acute migraine symptoms using beta blocker eye drops. The literature on beta blockers for acute migraine is reviewed. Oral beta blocker medication is not effective for acute migraine treatment. This is likely due to a relatively slow rate of achieving therapeutic plasma levels when taken orally. Topical beta blocker eye drops achieve therapeutic plasma levels within minutes of ocular administration which may explain their apparent effectiveness in relief of acute migraine symptoms. PMID:25211851

  20. [Need of risk reevaluation in morphine dependence in pain patients].

    PubMed

    Boureau, F; Luu, M; Koskas-Sergent, A S; Doubrere, J F

    1992-11-01

    It is commonly recognized than opioids analgesics have an major place in the treatment of pain. In spite of guidelines, opioids drugs remain underutilized in chronic cancer pain and acute severe pain. Among the possible factors, involved in the insufficient use of opioids drugs, is the fear (opiophoby) of physicians, nurses, patients and family to induce or to maintain an addiction. This review examines the potential of iatrogenic addiction. We will examined the place of morphine-like drugs in the treatment of severe acute pain and chronic cancer pain, the definition of dependency in pain patients, the assessment of the dependency potential in patients treated for pain. Available studies indicate that iatrogenic addiction is quite scarce and that the risk for a major tolerance is very small. Further studies will be necessary, since opioids analgesics may also be useful in some non-cancer chronic pain. PMID:1363796

  1. Atorvastatin attenuates the antinociceptive tolerance of morphine via nitric oxide dependent pathway in male mice.

    PubMed

    Hassanipour, Mahsa; Amini-Khoei, Hossein; Shafaroodi, Hamed; Shirzadian, Armin; Rahimi, Nastaran; Imran-Khan, Muhammad; Rezayat, Seyed-Mahdi; Dehpour, Ahmadreza

    2016-07-01

    The development of morphine-induced antinociceptive tolerance limits its therapeutic efficacy in pain management. Atorvastatin, or competitive inhibitor of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase, is mainstay agent in hypercholesterolemia treatment. Beyond the cholesterol-lowering activity, exploration of neuroprotective properties of this statin indicates its potential benefit in central nervous disorders. The aim of the present study was to assess the effects of atorvastatin in development and expression of morphine-induced analgesic tolerance in male mice and probable involvement of nitric oxide. Chronic and acute treatment with atorvastatin 10 and 20mg/kg, respectively, could alleviate morphine tolerance in development and expression phases. Chronic co-administration of nitric oxide synthase (NOS) inhibitors including L-NAME (non selective NOS inhibitor; 2mg/kg), aminoguanidine (selective inducible NOS inhibitor; 50mg/kg) and 7-NI (selective neuronal NOS inhibitor; 15mg/kg) with atorvastatin blocked the protective effect of atorvastatin in tolerance reversal. Moreover, reversing the atorvastatin effect was also observed in acute simultaneous treatment of L-NAME (5mg/kg) and aminoguanidine (100mg/kg) with atorvastatin. Co-treatment of guanylyl cyclase inhibitor, ODQ (chronic dose: 10mg/kg and acute dose: 20mg/kg) was associated with prevention of atorvastatin anti-tolerance properties. Our results revealed that the atorvastatin modulating role in morphine antinociceptive tolerance is mediated at least in part via nitric oxide in animal pain models of hot plate and tail flick. PMID:27381980

  2. Role of phosphodiesterase inhibitor Ibudilast in morphine-induced hippocampal injury

    PubMed Central

    Zhaleh, Mohsen; Panahi, Marzieh; Ghafurian Broujerdnia, Mehri; Ghorbani, Rostam; Ahmadi Angali, Kambiz; Saki, Ghasem

    2014-01-01

    Abstract: Background: Opioid drugs are used in the treatment of acute post-surgical pain and chronic pain, such as those associated with cancer. Opioid used is associated with complications such as analgesic tolerance, dependence and opioid abuse. The molecular mechanisms of unwanted opioid responses are varied but recent advances have highlighted elevations in pro-inflammatory cytokines and pro-inflammatory glial following chronic administration of morphine. In this study we investigated the neurodegenerative effects of morphine through its effects on Toll-Like Receptor 4 (TLR4) in the male rat hippocampus and evaluated the level of Interleukin-1 beta (IL-1β). Then we compared the difference between inhibitory effects on mu opioid receptors (by β-Funaltrexamine, β-FNA) and TLR4 (by Ibudilast). Subsequently, we assessed the amount of IL-1β and the number of granular cells in male rat hippocampus. Methods: Adult male rats (n=24) were treated with sucrose, morphine, Ibudilast (7.5 mg/kg) and β-FNA (20 mg/kg) for 30 days. Their brains were isolated and hemisected with one hippocampus for granular cell and the other used for IL-1 β immunoblotting. Results: Data showed that Ibudilast suppresses IL-1 β expression significantly more than β-FNA. The granular cell count displayed significant differences. Conclusions: Our results suggested that Ibudilast can be used for controlling and treatment of morphine-induced CNS inflammations or traumatic conditions. PMID:24121451

  3. Effect of chronic morphine administration on circulating dendritic cells in SIV-infected rhesus macaques.

    PubMed

    Cornwell, William D; Wagner, Wendeline; Lewis, Mark G; Fan, Xiaoxuan; Rappaport, Jay; Rogers, Thomas J

    2016-06-15

    We studied the effect of chronic morphine administration on the circulating dendritic cell population dynamics associated with SIV infection using rhesus macaques. Animals were either first infected with SIV and then given chronic morphine, or visa versa. SIV infection increased the numbers of myeloid DCs (mDCs), but morphine treatment attenuated this mDC expansion. In contrast, morphine increased the numbers of plasmacytoid DCs (pDCs) in SIV-infected animals. Finally, chronic morphine administration (no SIV) transiently increased the numbers of circulating pDCs. These results show that chronic morphine induces a significant alteration in the available circulating levels of critical antigen-presenting cells. PMID:27235346

  4. Treatment and pathogenesis of acute hyperkalemia

    PubMed Central

    Mushiyakh, Yelena; Dangaria, Harsh; Qavi, Shahbaz; Ali, Noorjahan; Pannone, John; Tompkins, David

    2012-01-01

    This article focuses on the pathogenesis, clinical manifestations, and various treatment modalities for acute hyperkalemia and presents a systematic approach to selecting a treatment strategy. Hyperkalemia, a life-threatening condition caused by extracellular potassium shift or decreased renal potassium excretion, usually presents with non-specific symptoms. Early recognition of moderate to severe hyperkalemia is vital in preventing fatal cardiac arrhythmias and muscle paralysis. Management of hyperkalemia includes the elimination of reversible causes (diet, medications), rapidly acting therapies that shift potassium into cells and block the cardiac membrane effects of hyperkalemia, and measures to facilitate removal of potassium from the body (saline diuresis, oral binding resins, and hemodialysis). Hyperkalemia with potassium level more than 6.5 mEq/L or EKG changes is a medical emergency and should be treated accordingly. Treatment should be started with calcium gluconate to stabilize cardiomyocyte membranes, followed by insulin injection, and b-agonists administration. Hemodialysis remains the most reliable method to remove potassium from the body and should be used in cases refractory to medical treatment. Prompt detection and proper treatment are crucial in preventing lethal outcomes. PMID:23882341

  5. Role of kappa and delta opioid receptors in mediating morphine-induced antinociception in morphine tolerant infant rats

    PubMed Central

    Stoller, Dawn C.; Sim-Selley, Laura J.; Smith, Forrest L.

    2011-01-01

    We have previously noted that the antinociceptive efficacy of morphine was significantly decreased in rat pups chronically infused with morphine from implanted osmotic minipumps. In this study, morphine was fully efficacious (i.e., 100% maximum possible effect, %MPE) in the 52 ºC tail-immersion test after a 72-h infusion from implanted saline-filled osmotic minipumps. However, administration of up to 1000 mg/kg s.c. morphine failed to elicit greater than a 27% MPE in rats infused with morphine at 2 mg/kg/h. Morphine was more efficacious when the water bath temperature was decreased to 49 ºC. Experiments were conducted to determine the mechanisms whereby chronic morphine administration leads to a decrease in antinociceptive efficacy. The kappa-opioid antagonist nor-binalorphimine completely blocked the antinociceptive effects of morphine in morphine-infused rat pups. The kappa agonist U50,488 elicited antinociception however, the requirement to use higher doses in morphine- than saline-infused rats indicates that kappa cross-tolerance was present. Thus, in tolerant rats the antinociceptive effects of high doses of morphine appear to be mediated through kappa-opioid receptors. The delta-opioid antagonist naltrindole was inactive in both treatment groups. DAMGO-stimulated [35S]GTPγS and [3H]naloxone binding reveal that the anatomical distribution of the mu-opioid receptor was consistent with that of the adult rat brain. In adult rats, the mu-opioid receptor is desensitized during morphine tolerance. However, desensitization was not evident in P17 rats based on the lack of significant decreases in [35S]GTPγS binding. Furthermore, [3H]naloxone binding indicated a lack of mu receptor downregulation in morphine-tolerant rat pups. PMID:17300766

  6. Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine.

    PubMed

    Zadina, James E; Nilges, Mark R; Morgenweck, Jenny; Zhang, Xing; Hackler, Laszlo; Fasold, Melita B

    2016-06-01

    Opioids acting at the mu opioid receptor (MOR) are the most effective analgesics, however adverse side effects severely limit their use. Of particular importance, abuse liability results in major medical, societal, and economic problems, respiratory depression is the cause of fatal overdoses, and tolerance complicates treatment and increases the risk of side effects. Motor and cognitive impairment are especially problematic for older adults. Despite the host of negative side effects, opioids such as morphine are commonly used for acute and chronic pain conditions. Separation of analgesia from unwanted effects has long been an unmet goal of opioid research. Novel MOR agonist structures may prove critical for greater success. Here we tested metabolically stable analogs of the endomorphins, endogenous opioids highly selective for the MOR. Compared to morphine, the analogs showed dramatically improved analgesia-to-side-effect ratios. At doses providing equal or greater antinociception than morphine in the rat, the analogs showed reduced a) respiratory depression, b) impairment of motor coordination, c) tolerance and hyperalgesia, d) glial p38/CGRP/P2X7 receptor signaling, and e) reward/abuse potential in both conditioned place preference and self-administration tests. Differential effects on glial activation indicate a mechanism for the relative lack of side effects by the analogs compared to morphine. The results suggest that endomorphin analogs described here could provide gold standard pain relief mediated by selective MOR activation, but with remarkably safer side effect profiles compared to opioids like morphine. PMID:26748051

  7. Chronic Morphine-Induced MicroRNA-124 Promotes Microglial Immunosuppression by Modulating P65 and TRAF6

    PubMed Central

    Qiu, Shuwei; Feng, Yimin; LeSage, Gene; Zhang, Ying; Stuart, Charles; He, Lei; Li, Yi; Caudle, Yi; Peng, Ying; Yin, Deling

    2014-01-01

    Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects including immunosuppression. However, the mechanisms are unclear. Toll-like receptors (TLRs) and acetylcholine (ACh) are widely expressed in the immune and nervous systems and play critical roles in immune responses. Here we show that morphine suppresses the innate immunity in microglia and bone marrow-derived macrophages (BMM) through differential regulation of TLRs and acetylcholinesterase (AChE). Either morphine or inhibition of ACh significantly promoted up-regulation of microRNA-124 (miR-124) in microglia, BMM, and in the mouse brain, where miR-124 mediates morphine inhibition of the innate immunity by directly targeting a subunit of NF-κB p65 and TNF receptor-associated factor 6 (TRAF6). Furthermore, transcription factors AP-1 and CREB inhibited miR-124, while p65 bound directly to promoters of miR-124, thereby enhancing miR-124 transcription. Moreover, acute morphine treatment transiently up-regulated the expression of p65 and phospho-p65 in both nucleus and cytoplasm priming the expression of miR-124, whereas long exposure of morphine maintained miR-124 expression which inhibited p65- and TRAF6-dependent TLR signaling. These data suggest that modulation of miRs is capable of preventing opioid-induced damage to microglia. PMID:25539811

  8. Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment

    PubMed Central

    Testoni, Pier Alberto

    2014-01-01

    Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches. PMID:25493002

  9. Valproate attenuates the development of morphine antinociceptive tolerance.

    PubMed

    Dobashi, Tamae; Tanabe, Serabi; Jin, Hisayo; Nishino, Takashi; Aoe, Tomohiko

    2010-11-19

    Morphine is a potent opioid analgesic. Repeated administration of morphine induces tolerance, thus reducing the effectiveness of analgesic treatment. Although some adjuvant analgesics can increase morphine analgesia, the precise molecular mechanism behind their effects remains unclear. Opioids bind to the mu opioid receptor (MOR). Morphine tolerance may be derived from alterations in the intracellular signal transduction after MOR activation. Chronic morphine treatment activates glycogen synthase kinase 3β (GSK3β), whose inhibition diminishes morphine tolerance. Valproate is widely prescribed as an anticonvulsant and a mood stabilizer for bipolar disorders because it increases the amount of γ-aminobutyric acid (GABA) in the central nervous system. Although the activation of GABAergic neurons may be responsible for the chief pharmacologic effect of valproate, recent studies have shown that valproate also suppresses GSK3β activity. We examined the effect of valproate on the development of morphine antinociceptive tolerance in a mouse model of thermal injury. Mice were treated with morphine alone or with morphine and valproate twice daily for 5 days. The resulting antinociceptive effects were assessed using a hot plate test. While mice treated with morphine developed tolerance, co-administration of valproate attenuated the development of tolerance and impaired the activation of GSK3β in mice brains. Valproate alone did not show analgesic effects; nevertheless, it functioned as an adjuvant analgesic to prevent the development of morphine tolerance. These results suggest that the modulation of GSK3β activity by valproate may be useful and may play a role in the prevention of morphine tolerance. PMID:20816918

  10. Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

    PubMed

    Denier, Niklaus; Schmidt, André; Gerber, Hana; Vogel, Marc; Huber, Christian G; Lang, Undine E; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan

    2015-12-01

    Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction. PMID:26441146

  11. Treatment of acute opioid withdrawal with ibogaine.

    PubMed

    Alper, K R; Lotsof, H S; Frenken, G M; Luciano, D J; Bastiaans, J

    1999-01-01

    Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty-three cases of treatments for the indication of opioid detoxification performed in non-medical settings under open label conditions are summarized involving an average daily use of heroin of .64 +/- .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72-hour period of posttreatment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting. PMID:10506904

  12. Treatment of acute bronchospasm in urban populations.

    PubMed

    Gaines, Beverly M

    2005-12-01

    Many urban patients, including minority groups and children, continue to live in poor urban settings. Poor urban environments provide a complex mix of stressors that can exacerbate asthma and increase exacerbations. Although care is available, many minority patients have English language and communication barriers, facts that impede their access to providers and care facilities. Medications for asthma are available to these patients, and strategies to minimize stressors are in place, but implementation and delivery in an urban setting can be a problem. Asthma management strategies coupled with new formulations of asthma medications, such as levalbuterol, can significantly reduce asthma symptoms during acute bronchospasm. In addition to offering the optimal treatment for asthma, broader strategies for reducing minority disparities are required if significant inroads are to be made in addressing problems faced by urban patients. PMID:19667713

  13. Treatment of Sporadic Acute Puerperal Mastitis

    PubMed Central

    Barton, John R.

    1996-01-01

    Objective: The purposes of this study were to compare the efficacy of amoxicillin and cephradine for the treatment of sporadic acute puerperal mastitis (SAPM) and to evaluate the microbiology and clinical parameters of this infection. Methods: We conducted a prospective, randomized, single-blinded study comparing amoxicillin, 500 mg orally q 8 h for 7 days, and cephradine, 500 mg orally q 6 h for 7 days. The diagnostic criteria for SAPM included a temperature of ≥37.56℃ (≥99.6℉) and erythema and tenderness of the breast(s). Results: Twenty-seven consecutive outpatients with SAPM were evaluated for admission to the study, and 25 of these were enrolled. The mean temperature at enrollment was 38.17℃ (100.7℉), with a mean WBC count of 11,440/μl. The most frequent bacterial isolates from expressed milk were Staphylococcus aureus (7), staphylococcal species (coagulase negative) (8), and α-hemolytic streptococci (4). There were no significant differences between the 2 antibiotic regimens in cure rate, mean days to resolution of symptoms, or recurrence within 30 days. Both of the treatment failures and 1 of the 3 recurrences within 30 days were amoxicillin-treated patients whose cultures grew S. aureus. Conclusions: Oral amoxicillin and cephradine appear equally effective in the treatment of SAPM. Staphylococci were the most frequent isolates from the milk of women with mastitis. PMID:18476075

  14. Effect of postoperative extradural morphine on lower urinary tract function.

    PubMed

    Husted, S; Djurhuus, J C; Husegaard, H C; Jepsen, J; Mortensen, J

    1985-02-01

    The effect of postoperative extradurally administered morphine on lower urinary tract function was studied in female patients undergoing uterine surgery. Urodynamic measurements were made on the day before and on the day after the operation, using a DISA 2-channel carbon dioxide (CO2) cystomictrograph. In ten patients without postoperative urinary retention no changes in cystometry were found during morphine administration, while two patients who developed acute urinary retention had a marked increase in bladder capacity and of detrusor pressure. In contrast, the urethral pressure profile was unchanged in both groups of patients. Intravenously administered naloxone tended to normalize the bladder capacity in the patients with urinary retention. These findings seem to indicate a marked effect in some patients of extradurally administered morphine and the acute urinary retention, following morphine administration, may be treated with naloxone. PMID:3976331

  15. Methadone Reverses Analgesic Tolerance Induced by Morphine Pretreatment

    PubMed Central

    Posa, Luca; Accarie, Alison; Marie, Nicolas

    2016-01-01

    Background: Opiates such as morphine are the most powerful analgesics, but their protracted use is restrained by the development of tolerance to analgesic effects. Recent works suggest that tolerance to morphine might be due to its inability to promote mu opioid receptor endocytosis, and the co-injection of morphine with a mu opioid receptor internalizing agonist like [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin reduces tolerance to morphine. So far, no studies have been conducted to evaluate the ability of methadone to reduce morphine tolerance in morphine-pretreated animals, a treatment sequence that could be encountered in opiate rotation protocol. We investigated the ability of methadone (a mu opioid receptor internalizing agonist used in therapy) to reverse morphine tolerance and the associated cellular mechanisms in the periaqueductal gray matter, a region involved in pain control. Methods: We measured analgesic response following a challenge dose of morphine in the hot plate test and investigated regulation of mu opioid receptor (coupling and endocytosis) and some cellular mechanisms involved in tolerance such as adenylate cyclase superactivation and changes in N-methyl-d-aspartate receptor subunits expression and phosphorylation state. Results: A chronic treatment with morphine promoted tolerance to its analgesic effects and was associated with a lack of mu opioid receptor endocytosis, adenylate cyclase overshoot, NR2A and NR2B downregulation, and phosphorylation of NR1. We reported that a methadone treatment in morphine-treated mice reversed morphine tolerance to analgesia by promoting mu opioid receptor endocytosis and blocking cellular mechanisms of tolerance. Conclusions: Our data might lead to rational strategies to tackle opiate tolerance in the frame of opiate rotation. PMID:26390873

  16. Pterostilbene as treatment for severe acute pancreatitis.

    PubMed

    Lin, Y J; Ding, Y; Wu, J; Ning, B T

    2016-01-01

    Acute pancreatitis (AP) has a fast onset and progression, which lead to an unfavorable prognosis. Therefore, the development of novel drugs for its treatment is critical. As a homologous derivative of resveratrol, pterostilbene exerts a variety of effects including anti-inflammatory, antioxidant, and antitumor effects. This study investigated the potential of pterostilbene for treatment of severe AP (SAP) and related mechanisms. Effects of pterostilbene were evaluated in a Wistar rat model of AP. Serum levels of amylase (AMY), creatinine (Cr), and alanine aminotransferase (ALT) were quantified. Furthermore, serum levels of tumor necrosis factor (TNF)-a and interleukin (IL)-1b were quantified using enzyme-linked immunosorbent assay. Nuclear factor (NF)-kB expression in pancreatic tissues was quantified by real-time PCR and western blotting. The production of reactive oxygen species (ROS) was determined using a spectrometer, while superoxide dismutase (SOD) activity was assayed. In the AP rat model, the expression of inflammatory markers TNF-a and IL-1b, expression of NF-kB, and serum indices (AMY, Cr, and ALT) increased compared to the corresponding levels in the control group (P < 0.05). Pterostilbene reduced serum levels of TNF-a and IL-1b; decreased NF-kB gene expression, serum indices, and ROS generation; and increased SOD activity in a dose-dependent manner. In conclusion, pterostilbene can alleviate SAP-induced tissue damage by decreasing the inflammatory response and by promoting antioxidation leading to the protection of pancreatic tissues. PMID:27525946

  17. Endovascular treatment of acute ischemic stroke.

    PubMed

    Leslie-Mazwi, Thabele; Rabinov, James; Hirsch, Joshua A

    2016-01-01

    Endovascular thrombectomy is an effective treatment for major acute ischemic stroke syndromes caused by major anterior circulation artery occlusions (commonly referred to as large vessel occlusion) and is superior to intravenous thrombolysis and medical management. Treatment should occur as quickly as is reasonably possible. All patients with moderate to severe symptoms (National Institutes of Health stroke scale >8) and a treatable occlusion should be considered. The use of neuroimaging is critical to exclude hemorrhage and large ischemic cores. Very shortly after stroke onset (<3 hours) computed tomography (CT) and CT angiography provide sufficient information to proceed; diffusion magnetic resonance imaging (MRI) is less reliable during this early stage. After 3 hours from onset diffusion MRI is the most reliable method to define ischemic core size and should be used in centers that can offer it rapidly. Recanalization is highly effective with a stentriever or using a direct aspiration technique, with the patient awake or under conscious sedation rather than general anesthesia, if it may be performed safely. After thrombectomy the patient should be admitted to an intensive care setting and inpatient rehabilitation undertaken as soon as feasible. Patient outcomes should be assessed at 3 months, preferably using the modified Rankin score. PMID:27430469

  18. Chronic morphine induces up-regulation of the pro-apoptotic Fas receptor and down-regulation of the anti-apoptotic Bcl-2 oncoprotein in rat brain

    PubMed Central

    Boronat, M Assumpció; García-Fuster, M Julia; García-Sevilla, Jesús A

    2001-01-01

    This study was designed to assess the influence of activation and blockade of the endogenous opioid system in the brain on two key proteins involved in the regulation of programmed cell death: the pro-apoptotic Fas receptor and the anti-apoptotic Bcl-2 oncoprotein. The acute treatment of rats with the μ-opioid receptor agonist morphine (3 – 30 mg kg−1, i.p., 2 h) did not modify the immunodensity of Fas or Bcl-2 proteins in the cerebral cortex. Similarly, the acute treatment with low and high doses of the antagonist naloxone (1 and 100 mg kg−1, i.p., 2 h) did not alter Fas or Bcl-2 protein expression in brain cortex. These results discounted a tonic regulation through opioid receptors on Fas and Bcl-2 proteins in rat brain. Chronic morphine (10 – 100 mg kg−1, 5 days, and 10 mg kg−1, 13 days) induced marked increases (47 – 123%) in the immunodensity of Fas receptor in the cerebral cortex. In contrast, chronic morphine (5 and 13 days) decreased the immunodensity of Bcl-2 protein (15 – 30%) in brain cortex. Chronic naloxone (10 mg kg−1, 13 days) did not alter the immunodensities of Fas and Bcl-2 proteins in the cerebral cortex. The concurrent chronic treatment (13 days) of naloxone (10 mg kg−1) and morphine (10 mg kg−1) completely prevented the morphine-induced increase in Fas receptor and decrease in Bcl-2 protein immunoreactivities in the cerebral cortex. The results indicate that morphine, through the sustained activation of opioid receptors, can promote abnormal programmed cell death by enhancing the expression of pro-apoptotic Fas receptor protein and damping the expression of anti-apoptotic Bcl-2 oncoprotein. PMID:11704646

  19. Treatment of acute, severe epigastric/chest pain in a patient with stomach cancer following gastrectomy: A case report

    PubMed Central

    ZAPOROWSKA-STACHOWIAK, IWONA; GORZELIŃSKA, LIDIA; SOPATA, MACIEJ; ŁUCZAK, JACEK

    2015-01-01

    The treatment of acute chest pain can be a challenge in palliative care. Firstly, because acute chest pain is a symptom of a paucity of diseases, which makes diagnosis difficult and time consuming, while there is also a time constraint, due to the extreme suffering of the patient. Secondly, the condition of a patient with advanced cancer disease and co-morbidities does not always allow for required diagnostic procedures. The present report describes a case of acute, severe epigastric/chest pain in a patient with dynamic disease progression, who was receiving palliative care. This study also demonstrates that the pathophysiology of pain in a terminal patient may determine the treatment strategy. The patient in the present case was a 41-year-old male, who had previously undergone gastrectomy for stomach cancer, followed by postoperative chemotherapy. The patient was treated with palliative chemotherapy for metastases to the lungs, liver and lymph nodes, which led to the development of iatrogenic peripheral neuropathy. The patient was subsequently admitted to the Palliative Medicine In-patient Unit of the University Hospital of Lord’s Transfiguration (Poznan, Poland) with the complaint of acute epigastric and chest pain. An electrocardiogram, echocardiogram, chest and abdomen computerized tomography scan, esophagoduodenoscopy and laboratory analyses were performed to determine the source of the pain. The patient was treated with morphine sulfate, metoclopramide, midazolam, diazepam, acetaminophen, ketamine, hyoscine butylbromide, propofol, dexamethasone and amoxycillin, and received parenteral nutrition. As the source of pain remained unclear, a second esophagoduodenoscopy was performed to determine a diagnosis, resulting in pain relief. Thus, in the present case, esophagoduodenoscopy was diagnostic and therapeutic. Furthermore, although the treatment of acute chest pain may be a challenge in palliative care, the present study indicates that pain treatment should be

  20. Morphine: Myths and Reality

    MedlinePlus

    ... ve heard that Morphine has lots of side effects, and I feel bad enough already.” All opiates can cause nausea, drowsiness and constipation. However, all side effects will generally stop after a few days, as ...

  1. Empirical treatment of acute cystitis in women.

    PubMed

    Nicolle, Lindsay E

    2003-07-01

    Empirical antimicrobial treatment for acute cystitis in women requires continuing reassessment as the antimicrobial susceptibility of community isolates of Escherichia coli evolves. Current recommendations for 3 days trimethoprim or trimethoprim/sulphamethoxazole are compromised by increasing resistance of community E. coli to these agents. Fluoroquinolones are an alternate 3-day therapy, but increasing resistance is being reported from some countries, and widespread community use may promote resistance, limiting effectiveness of these agents for more serious infections. Alternate regimens supported by recent clinical trials suggest pivmecillinam given twice daily for 7 days is as effective as 3 days of quinolone therapy, while microbiological cure is 80% with 3 days therapy twice daily, and 90% with 3 days therapy thrice daily. Nitrofurantoin given for 7 days has a cure rate of 80-85%. Fosfomycin trometamol as a single dose has cure rates of 75-85%. All these agents are effective, but a compromise in efficacy or duration of therapy compared with current 3-day regimens may have to be considered. PMID:12842322

  2. [Intubation treatment of acute laryngeal obstruction: a case report].

    PubMed

    Guo, Xingguang; Liu, Shibo; Li, Huilian

    2015-11-01

    Acute laryngeal obstruction is one of the most common diseases in Department of ENT, and it can cause suffocation without prompt treatment. Methods by using Nasopharyngofiberoscope guided tracheal intubation treatment of a case of acute laryngeal obstruction patients in a timely manner. This method is well tolerated, less trauma, high success rate, in the shortest time to improve the patient's ventilation, for the next step of the treatment to win the time. PMID:26911075

  3. Hyperplastic polyps following treatment of acute gastric ulcers.

    PubMed

    Tanaka, J; Fujimoto, K; Iwakiri, R; Koyama, T; Sakata, H; Ohyama, T; Mizuguchi, M; Tokunaga, O

    1994-06-01

    Although hyperplastic polyps are the most common polyps of the stomach, the etiology of these polyps is not completely understood. We report a 61-year-old woman who developed gastric hyperplastic polyps following acute gastric lesions. She was admitted for endoscopic injection sclerotherapy of esophageal varices. After the end of sclerotherapy, acute gastric lesions developed. For treatment of the lesions, omeprazole was used for 8 weeks followed by famotidine for 8 weeks. At the end of the treatment, she developed multiple gastric hyperplastic polyps, suggesting that acute gastric lesions and/or treatment of the gastric lesions are related to the development of hyperplastic polyps in the stomach. PMID:7919626

  4. Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

    PubMed Central

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B.; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. PMID:24618941

  5. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    PubMed

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. PMID:24618941

  6. Analgesic efficacy of morphine applied topically to painful ulcers.

    PubMed

    Zeppetella, Giovambattista; Paul, James; Ribeiro, Maria D C

    2003-06-01

    The analgesic effects of morphine applied topically to painful ulcers was assessed in a randomized, double-blind, placebo-controlled, crossover pilot study of five patients with painful sacral sores. Patients were treated for two days with either 10 mg morphine sulfate or placebo (water for injection) applied topically to the ulcer. After a two-day wash-out period, patients were crossed over for a further two days of the alternative treatment. Patients were asked to rate analgesia using a visual analogue scale (VAS) and to document any local or systemic adverse effects. All patients reported lower VAS scores with morphine compared to placebo and no local or systemic adverse events attributable to morphine were noted by either patients or nursing staff. This pilot study suggests that morphine applied topically is an effective method of producing local analgesia, well tolerated by patients, and not associated with systemic adverse effects. PMID:12782436

  7. Epidural morphine for outpatients with severe anginal pain.

    PubMed Central

    Clemensen, S E; Thayssen, P; Hole, P

    1987-01-01

    Seven patients who had chronic coronary artery disease and had undergone coronary artery bypass surgery still suffered from anginal attacks several times daily despite optimal medical treatment. An epidural system of analgesia was implanted subcutaneously and treatment with epidural morphine started. The morphine was administered by the patients themselves or members of their family. During a median observation time of four months (range three to 11) all patients were free of pain while receiving this treatment. Images p476-a PMID:2435345

  8. [Thrombolytic treatment of acute myocardial infarct. 1].

    PubMed

    Soares-Costa, J T; Soares-Costa, T J; Gabriel, H M

    1998-05-01

    I-Rationale of thrombolytic therapy in acute myocardial infarction (AMI). II-Thrombolytic drugs. III-Effects of thrombolytic therapy on mortality. IV-Studies comparing the effects of various thrombolytic agents on mortality. PMID:9951051

  9. The effects of morphine and morphine conditioned context on 50 kHz ultrasonic vocalisation in rats.

    PubMed

    Hamed, Adam; Taracha, Ewa; Szyndler, Janusz; Krząścik, Paweł; Lehner, Małgorzata; Maciejak, Piotr; Skórzewska, Anna; Płaźnik, Adam

    2012-04-15

    The 50 kHz ultrasonic vocalisations (USVs) that are emitted by rats are dependent on activity of dopaminergic neurons projecting from the ventral tegmental area to the limbic and cortical structures. According to many experimental data, emission of the 50 kHz USV reflects a positive emotional state. The appetitive calls are also emitted in response to the administration of drugs of abuse, e.g., cocaine or amphetamine (AMPH), or in a reply to a positively conditioned context. However, there is no strong evidence in the literature that morphine can also modulate 50 kHz USVs. The aim of this paper is to study the effects of morphine and morphine-conditioned context on 50 kHz USVs, using spontaneously or drug-modulated 50 kHz USVs. Our results showed that acute administration of morphine to rats after withdrawal period inhibited the emission of 50 kHz USVs. The stimulating effect of morphine-conditioned context on 50 kHz USVs appeared on the post-withdrawal challenge day immediately before drug injection, 14 days after the last episode of morphine-induced context conditioning. The context-induced 50 kHz USVs can be used as a sensitive test for drug dependency. The current study also shows that 50 kHz USVs can be useful tool for studying the mechanisms of long lasting central effects of morphine. PMID:22326697

  10. Acute Lymphoblastic Leukemia (ALL) Treatment in Adults (Beyond the Basics)

    MedlinePlus

    ... 2016 UpToDate, Inc. Patient information: Acute lymphoblastic leukemia (ALL) treatment in adults (Beyond the Basics) Author Richard ... the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of ...

  11. Renal colic in adults: NSAIDs and morphine are effective for pain relief.

    PubMed

    2009-10-01

    (1) Renal colic is an acute syndrome involving unilateral flank pain, linked to an obstruction in the upper urinary tract. The pain is often intense. After having considered other diagnoses and checked for signs of complication (fever, oligoanuria), the first step is to control the pain; (2) Which non-invasive treatments have a positive risk-benefit balance in relieving this type of pain? To answer this question, we reviewed the available evidence, based on the standard Prescrire methodology; (3) According to a meta-analysis of 20 trials, nonsteroidal antiinflammatory drugs (NSAIDs) and strong opioid analgesics have comparable efficacy. The most widely studied NSAID is diclofenac, given intramuscularly at a dose of 50 mg or 75 mg. Pethidine is the best-assessed strong opioid, given intramuscularly at a dose of 50 mg to 100 mg, which corresponds to about 5 mg to 10 mg of morphine. Morphine is given intravenously; subcutaneous administration is an alternative although it has not been evaluated in renal colic; (4) In clinical trials, NSAIDs were associated with fewer adverse effects than opioids, which cause vomiting in about 20% of patients (versus about 6% with an NSAID); (5) NSAIDs expose patients to a risk of functional renal impairment, especially in patients with heart failure, renal artery stenosis, dehydration, renal impairment or ongoing treatment with a nephrotoxic drug, and the very elderly. NSAIDs should never be used during pregnancy; (6) According to one trial in 130 patients, the analgesic effect of the morphine and NSAID combination was greater than either agent used alone, in about 10% of patients; (7) Paracetamol has not been evaluated in comparative trials of renal colic, even for moderate pain; (8) Scopolamine is the only antispasmodic to have been evaluated in a comparative trial. Adding scopolamine to morphine did not seem to provide additional efficacy; (9) Other drugs, which have not been adequately tested as of early 2009, have no documented

  12. Acute dental pain, Part II: Diagnosis and emergency treatment.

    PubMed

    Antonelli, J R

    1990-09-01

    Part II of this two-part series differentiates and explores endodontic-related emergencies with reversible and irreversible pulpitis. Indications and contra-indications for vital pulp therapy are explained, and treatment is outlined. The inflammatory process involved in irreversible pulpal disease is summarized, and the clinical signs, symptoms, and treatment of irreversible pulpitis (with and without acute periradicular involvement, with pulp necrosis, and acute periradicular abscess with and without cellulitis) are discussed. PMID:2097056

  13. [Galvanic current in the conservative treatment of acute pancreatitis].

    PubMed

    Alekseenko, A V; Iftodiĭ, A G; Stoliar, V F

    1990-10-01

    Experiments were conducted on 42 adult dogs with a model of acute pancreatitis to study the degree of antibiotic storage in the pancreatic tissue in different variants of intralesional+ electrophoresis. Optimum concentration of the antibiotic was produced in transverse galvanization of the zone of the pancreas. Clinical observations over 63 patients with various forms of acute pancreatitis bear evidence that the method raises the efficacy of nonoperative treatment in the oedematous stage of the process and reduces the duration of treatment. PMID:2283730

  14. [Acute pain in children and its treatment].

    PubMed

    Dalens, B

    1991-01-01

    Pain in paediatrics has long been underestimated. The numerous scientific studies carried out during the last decade show that its existence can no longer be doubted: in fact, pain already exists during the neonatal period, and probably throughout the last trimester of gestation as well. Pain pathways mature during the embryonic period and peripheral receptors develop between the 7th and 20th week. A-delta and C fibers, as well as spinal roots and nerves, are completely differentiated before the end of the second month. The development of specific neurotransmitters and thalamic and cortical dendritic branching occurs later on; it is well enough developed to allow perception of painful stimuli (slow or protopathic component) from the beginning of the foetal period onwards. The discriminative rapid component develops in parallel to myelinisation, and the psycho-affective component, which requires a long and complex learning process, will not be fully operative until the end of puberty. Assessing pain, already a difficult task in the adult, is all the more so in children because of lesser verbal communicative capabilities, difficulty in handling abstract concepts, lack of experience of painful stimuli to make comparisons, and ignorance of their body image. In the very young child, diagnosing pain relies on suggestive circumstances, and an altered behaviour, knowing that no one symptom in pathognomonic. As the child grows up, methods for self-assessment of pain become usable, such as coloured scales and simplified verbal scales. However, behavioural tests remain the mainstay until the prepubertal period. The treatment of acute pain requires a reasoned approach which takes into account the state of the child, that of the aetiological investigations, the likely course of the lesions, as well as the patient's analgesic requirements. Therapeutic means do not differ from those for adult patients; however, the differences of distribution of body water, the small

  15. Colon Cancer After Acute Diverticulitis Treatment

    PubMed Central

    Oh, Kwang Hoon; Kim, Eun Jung; Lee, Je Hoon; Choi, Kyu Un; Han, Myung Sik; Ahn, Jae Hong; Cheon, Gab Jin

    2013-01-01

    Diverticulitis is the most common clinical complication of diverticular disease, affecting 10-25% of the patients with diverticula. The prevalences of diverticulitis and colon cancer tend to increase with age and are higher in industrialized countries. Consequently, diverticulitis and colon cancer have been reported to have similar epidemiological characteristics. However, the relationship between these diseases remains controversial, as is the performance of routine colonoscopy after an episode of diverticulitis to exclude colon cancer. Recently, we experienced three cases of colon cancer after treating acute diverticulitis, based on which we suggest the importance of follow-up colonoscopy after acute diverticulitis. PMID:24032118

  16. D-cycloserine facilitates extinction of naloxone-induced conditioned place aversion in morphine-dependent rats

    PubMed Central

    Myers, Karyn M.; Carlezon, William A.

    2016-01-01

    BACKGROUND Cues paired with drug administration trigger relapse to drug-seeking by inducing conditioned drug craving and withdrawal. Because drug cues hinder abstinence in addicts, therapies that reduce responsiveness to drug cues might facilitate rehabilitation. Extinction is a means of reducing conditioned responses and involves exposure to the conditioned stimulus (CS) in the absence of the unconditioned stimulus (US) with which it was paired previously. We examined conditioned withdrawal extinction using naloxone-induced conditioned place aversion (CPA) in morphine-dependent rats. METHOD Morphine-dependent rats were trained to associate an environment with naloxone-precipitated withdrawal. Subsequently they received extinction training in which they were confined in the previously naloxone-paired environment in the absence of acute withdrawal. In some rats, the NMDA receptor partial agonist D-cycloserine (DCS) was administered prior to extinction training. RESULTS Morphine withdrawal-induced CPA persists in the absence of extinction training. Administration of DCS prior to extinction training facilitates extinction. CONCLUSIONS DCS facilitates extinction of morphine withdrawal-associated place aversion. This effect is qualitatively similar to the effect of DCS on extinction of conditioned fear, raising the possibility of common neural mechanisms. This work extends our understanding of drug cue responsivity and provides a rationale for the development of extinction-based treatments for addiction. PMID:19782965

  17. STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance.

    PubMed

    Kim, Yoon-Jung; Kang, Young; Park, Hye-Yeon; Lee, Jae-Ran; Yu, Dae-Yeul; Murata, Takuya; Gondo, Yoichi; Hwang, Jung Hwan; Kim, Yong-Hoon; Lee, Chul-Ho; Rhee, Myungchull; Han, Pyung-Lim; Chung, Bong-Hyun; Lee, Hyun-Jun; Kim, Kyoung-Shim

    2016-01-01

    Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEP(C230X-/-) mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEP(C230X-/-) mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine. PMID:26915673

  18. Assessment of morphine-induced hyperalgesia and analgesic tolerance in mice using thermal and mechanical nociceptive modalities.

    PubMed

    Elhabazi, Khadija; Ayachi, Safia; Ilien, Brigitte; Simonin, Frédéric

    2014-01-01

    Opioid-induced hyperalgesia and tolerance severely impact the clinical efficacy of opiates as pain relievers in animals and humans. The molecular mechanisms underlying both phenomena are not well understood and their elucidation should benefit from the study of animal models and from the design of appropriate experimental protocols. We describe here a methodological approach for inducing, recording and quantifying morphine-induced hyperalgesia as well as for evidencing analgesic tolerance, using the tail-immersion and tail pressure tests in wild-type mice. As shown in the video, the protocol is divided into five sequential steps. Handling and habituation phases allow a safe determination of the basal nociceptive response of the animals. Chronic morphine administration induces significant hyperalgesia as shown by an increase in both thermal and mechanical sensitivity, whereas the comparison of analgesia time-courses after acute or repeated morphine treatment clearly indicates the development of tolerance manifested by a decline in analgesic response amplitude. This protocol may be similarly adapted to genetically modified mice in order to evaluate the role of individual genes in the modulation of nociception and morphine analgesia. It also provides a model system to investigate the effectiveness of potential therapeutic agents to improve opiate analgesic efficacy. PMID:25145878

  19. Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

    PubMed Central

    Elhabazi, Khadija; Ayachi, Safia; Ilien, Brigitte; Simonin, Frédéric

    2014-01-01

    Opioid-induced hyperalgesia and tolerance severely impact the clinical efficacy of opiates as pain relievers in animals and humans. The molecular mechanisms underlying both phenomena are not well understood and their elucidation should benefit from the study of animal models and from the design of appropriate experimental protocols. We describe here a methodological approach for inducing, recording and quantifying morphine-induced hyperalgesia as well as for evidencing analgesic tolerance, using the tail-immersion and tail pressure tests in wild-type mice. As shown in the video, the protocol is divided into five sequential steps. Handling and habituation phases allow a safe determination of the basal nociceptive response of the animals. Chronic morphine administration induces significant hyperalgesia as shown by an increase in both thermal and mechanical sensitivity, whereas the comparison of analgesia time-courses after acute or repeated morphine treatment clearly indicates the development of tolerance manifested by a decline in analgesic response amplitude. This protocol may be similarly adapted to genetically modified mice in order to evaluate the role of individual genes in the modulation of nociception and morphine analgesia. It also provides a model system to investigate the effectiveness of potential therapeutic agents to improve opiate analgesic efficacy. PMID:25145878

  20. STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance

    PubMed Central

    Kim, Yoon-Jung; Kang, Young; Park, Hye-Yeon; Lee, Jae-Ran; Yu, Dae-Yeul; Murata, Takuya; Gondo, Yoichi; Hwang, Jung Hwan; Kim, Yong-Hoon; Lee, Chul-Ho; Rhee, Myungchull; Han, Pyung-Lim; Chung, Bong-Hyun; Lee, Hyun-Jun; Kim, Kyoung-Shim

    2016-01-01

    Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEPC230X−/− mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEPC230X−/− mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine. PMID:26915673

  1. Extracorporeal photopheresis in prevention and treatment of acute GVHD.

    PubMed

    Kitko, Carrie L; Levine, John E

    2015-04-01

    Acute graft versus host disease (GVHD), a common complication after allogeneic hematopoietic cell transplantation (HCT), occurs in as many as 70% of recipients of this life saving treatment. Front line therapy for GVHD with corticosteroids will fail in up to 40% of patients, which leads to high morbidity and mortality. Traditional prevention and treatment strategies have focused on reducing alloreactivity, typically with therapy to reduce cytotoxic T-cell function. Emerging evidence exists that promotion of regularly T-cell function, through treatments such as extracorporeal photopheresis, is effective for GVHD treatment and has potential for prevention as well. This review will focus on literature reporting the success of ECP for steroid refractory acute GVHD and the potential for delivery of ECP in the early pre and post-transplant periods that shows promise as a less immunosuppressive strategy to reduce rates of acute GVHD. PMID:25748231

  2. What do patients want from acute migraine treatment?

    PubMed

    Gallagher, Rm

    2004-01-01

    Clinical observations have shown that migraine is a progressive disorder, both within an acute attack, and within the disease itself. Rates of diagnosis for migraine have increased in the last decade, but more than half of migraineurs remain undiagnosed. Patient expectations of migraine therapies have also increased (patients require rapid and sustained pain relief with a treatment that has good tolerability), and can differ greatly from those of physicians. Management decisions should be made with these expectations in mind, to enhance patient outcomes and compliance with treatment. Improved understanding of acute migraine attack pathophysiology has led to the strategy of early treatment to modify both the progression of the current attack and, potentially, the progression of the disease itself in the individual. The triptans are effective acute migraine therapies. Each agent has its own distinct profile of efficacy and tolerability, enabling individualization of treatment. PMID:15595989

  3. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed. PMID:27018033

  4. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    ERIC Educational Resources Information Center

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  5. Treatment of acute silicoproteinosis by whole-lung lavage.

    PubMed

    Stafford, Marshall; Cappa, Anthony; Weyant, Michael; Lara, Abigail; Ellis, James; Weitzel, Nathaen S; Puskas, Ferenc

    2013-06-01

    Acute silicoproteinosis is a rare disease that occurs following a heavy inhalational exposure to silica dusts. Clinically, it resembles pulmonary alveolar proteinosis (PAP); silica exposure is thought to be a cause of secondary PAP. We describe a patient with biopsy-confirmed acute silicoproteinosis whose course was complicated by acute hypoxemic respiratory failure requiring mechanical ventilation. Without clinical improvement despite antibiotic and steroid treatment, the patient was scheduled for whole-lung lavage under general anesthesia. Anesthetic challenges included double-lumen tube placement and single-lung ventilation in a hypoxic patient, facilitating lung lavage, and protecting the contralateral lung from catastrophic spillage. PMID:23632425

  6. Persistent Pain Model Reveals Sex Difference in Morphine Potency

    PubMed Central

    Wang, Xiaoya; Traub, Richard J.; Murphy, Anne Z.

    2010-01-01

    Central or systemic administration of agonists directed at the mu or delta opiate receptors generally produce a greater degree of analgesia in males than in females. To date, the majority of studies examining sex based differences in opioid analgesia have employed acute noxious stimuli (i.e. tail-flick and hot plate test); thus, the potential dimorphic response of centrally acting opiates in the alleviation of persistent inflammatory pain is not well established. In the present study, right hindpaw withdrawal latency (PWL) to radiant thermal stimuli was measured in intact male and cycling female Sprague-Dawley rats before and after unilateral hindpaw injection of the inflammatory agent complete Freund’s adjuvant (CFA). Control animals received intraplantar injection of saline. Twenty four hours after CFA or saline injection, animals received either saline or morphine bisulfate (0.5 – 15 mg/kg; s.c.). Separate groups of control or inflamed animals were tested on their responsiveness to morphine at 7, 14 and 21 days post-CFA or saline. No sex differences were noted for baseline PWLs, and females displayed slightly less thermal hyperalgesia at 24 hrs post-CFA. At all morphine doses administered, both the antihyperalgesic effects of morphine in the inflamed animals, and the antinociceptive effects of morphine in control animals, were significantly greater in males in comparison to females. Similarly, in males, the antihyperalgesic effects of morphine increased significantly at 7–21 days post-CFA; no significant shift in morphine potency was noted for females. These studies demonstrate sex-based differences in the effects of morphine on thermal hyperalgesia in a model of persistent inflammatory pain. PMID:16497818

  7. Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone.

    PubMed

    Aminian, Atefeh; Javadi, Shiva; Rahimian, Reza; Dehpour, Ahmad Reza; Asadi Amoli, Fahimeh; Moghaddas, Payman; Ejtemaei Mehr, Shahram

    2016-07-01

    Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent. Morphine and other opioids are also used extensively in different types of cancer for the clinical management of pain associated with local or metastatic neoplastic lesions. In addition to its analgesic effects, morphine has also been reported to possess potential immunomodulatory and antioxidant properties. Herein, we investigated the effects of morphine in a rat model of cisplatin-induced nephrotoxicity. Following administration of a single dose of cisplatin (5 mg/kg), animals received intraperitoneal injections of morphine (5 mg/kg/day) and/or naltrexone (20 mg/kg/day), an opioid antagonist, for 5 days. Cisplatin-induced nephrotoxicity was detected by a significant increase in plasma urea and creatinine levels in addition to alterations in kidney tissue morphology. Levels of TNF-α and IL-1β were significantly increased in the renal tissue in cisplatin group. Moreover, glutathione (GSH) concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals. Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that concomitant treatment with morphine might intensify cisplatin-induced renal damage in rats. These findings suggest that morphine and other opioids should be administered cautiously in patients receiving cisplatin chemotherapy. PMID:27424012

  8. Faropenem medoxomil: a treatment option in acute bacterial rhinosinusitis.

    PubMed

    Hadley, James A; Tillotson, Glenn S; Tosiello, Robert; Echols, Roger M

    2006-12-01

    Faropenem medoxomil is the first oral penem in a new class of beta-lactam antibiotics. Faropenem medoxomil has excellent in vitro activity against Streptococcus pneumoniae, Haemophilus influenzae and other key pathogens implicated in acute bacterial rhinosinusitis. Clinical studies have demonstrated that, in the treatment of acute bacterial rhinosinusitis in adults, 7 days of treatment with faropenem medoxomil is as clinically and bacteriologically effective as 10 days of treatment with cefuroxime axetil. One study showed faropenem medoxomil to be superior to cefuroxime axetil. Overall, the safety profile of faropenem medoxomil is similar to that of most comparators. Specifically, the minimal impact of faropenem medoxomil on the gastrointestinal flora leads to less diarrhea and other adverse events than coamoxicillin-clavulanate. Faropenem medoxomil has almost no drug-drug interactions and little requirement for dosage adjustments in the typical acute rhinosinusitis population. PMID:17181408

  9. Might adrenergic alpha2C-agonists/alpha2A-antagonists become novel therapeutic tools for pain treatment with morphine?

    PubMed

    Cardinaletti, Claudia; Mattioli, Laura; Ghelfi, Francesca; Del Bello, Fabio; Giannella, Mario; Bruzzone, Ariana; Paris, Hervé; Perfumi, Marina; Piergentili, Alessandro; Quaglia, Wilma; Pigini, Maria

    2009-11-26

    The imidazoline nucleus linked in position 2 via an oxyethylene bridge to a phenyl ring carrying an ortho substituent of moderate steric bulk provided alpha(2)-adrenergic (AR) ligands endowed with significant alpha(2C)-agonism/alpha(2A)-antagonism. Similar behavior was displayed by cirazoline (12). For their positive morphine analgesia modulation (due to alpha(2C)-AR stimulation) and sedation overcoming (due to alpha(2A)-AR antagonism), 8 and 11 might be useful as adjuvant agents in the management of pain with morphine. PMID:19886609

  10. Dipeptides delay the onset of morphine withdrawal in the mouse.

    PubMed

    Kovács, G L; Szontágh, L; Baláspiri, L; Telegdy, G

    1984-01-01

    The effect of dipeptides was studied on naloxone-precipitated morphine withdrawal in the mouse. In accordance with previous data, s.c. treatment with Z-prolyl-D-leucine delayed the onset of withdrawal jumpings . Replacement of L-proline by L-glutamate or L-pyroglutamate resulted in dipeptides which were more potent in morphine withdrawal than was Z-prolyl-D-leucine. PMID:6540034

  11. Comparison of two main treatment modalities for acute ankle sprain

    PubMed Central

    Bilgic, Serkan; Durusu, Murat; Aliyev, Bahtiyar; Akpancar, Serkan; Ersen, Omer; Yasar, S.Mehmet; Ardic, Sukru

    2015-01-01

    Objective: Acute ankle sprains are one of the most common injuries in emergency departments. Immobilization is widely accepted as the basic treatment modality for acute ankle sprains; however, immobilization method remains controversial. In this study, we aimed to compare two treatment modalities: splint and elastic bandage for the management of acute ankle sprains. Methods: This prospective study was conducted in the emergency department. Fifty-one consecutive patients who were admitted to the emergency department owing to the complaint of ankle sprain and who were treated with an elastic bandage or a splint were included in the study. After bone injury was ruled out, treatment choice was left to the on-shift physicians’ discretion. The extent of edema was evaluated before and after the treatment by using a small, graduated container filled with warm water. Volume differences were calculated by immersing both lower extremities in a container filled to a constant level. Pain was evaluated using the visual analogue scale. Results: There were 25 patients in the elastic bandage group and 26 patients in the splint group. VAS scores of these groups before and after the treatment were similar. Although edema size before and after the treatment were similar between the groups, edema size reduction was significantly more in the elastic bandage group [p=0,025]. Conclusions: This study showed that treatment of acute ankle sprains with an elastic bandage was more effective than splint in reducing edema. Therefore, an elastic bandage could be preferred over a splint for the treatment of acute ankle sprains. PMID:26870123

  12. Diagnosis and treatment of acute extremity compartment syndrome.

    PubMed

    von Keudell, Arvind G; Weaver, Michael J; Appleton, Paul T; Appelton, Paul T; Bae, Donald S; Dyer, George S M; Heng, Marilyn; Jupiter, Jesse B; Vrahas, Mark S

    2015-09-26

    Acute compartment syndrome of the extremities is well known, but diagnosis can be challenging. Ineffective treatment can have devastating consequences, such as permanent dysaesthesia, ischaemic contractures, muscle dysfunction, loss of limb, and even loss of life. Despite many studies, there is no consensus about the way in which acute extremity compartment syndromes should be diagnosed. Many surgeons suggest continuous monitoring of intracompartmental pressure for all patients who have high-risk extremity injuries, whereas others suggest aggressive surgical intervention if acute compartment syndrome is even suspected. Although surgical fasciotomy might reduce intracompartmental pressure, this procedure also carries the risk of long-term complications. In this paper in The Lancet Series about emergency surgery we summarise the available data on acute extremity compartment syndrome of the upper and lower extremities in adults and children, discuss the underlying pathophysiology, and propose a clinical guideline based on the available data. PMID:26460664

  13. Use of morphine in cholescintigraphy for obstructive cholecystitis

    SciTech Connect

    Kim, E.E.; Nguyen, M.; Pjura, G.; Pollack, M.; Gobuty, A.

    1985-05-01

    Non-visualization of the gallbladder (GB) during the first hour of cholescintigraphy is observed in cystic duct obstruction (e.g. in acute cholecystitis) but may also occur in chronic cholecystitis, hepatocellular disease, alcoholism and prolonged total parenteral nutrition. Low dose morphine is shown to improve the specificity of the diagnosis of acute cholecystitis (from 85% to 100%) with no loss in sensitivity (98%) at a small cost in terms of additional study time. The authors reviewed 27 selected cholescintigraphic examinations augmented by intravenous (IV) morphine (0.04 mg/Kg). Of the 16 cases with persistent nonvisualization of the GB, ultrasound revealed gallstones in 5 cases, sludge in 4, acalculous cholecystitis in 3, one distended GB, one contracted GB and 2 normal GB's. Of the 4 patients taken to surgery, one with gallstones and one with acalculous cholecystitis were confirmed to have acute cholecystitis while another with gallstones had chronic cholecystitis and the final patient, who was sonographically normal, presented a single common duct stone. The authors conclude that the use of IV morphine is an effective adjunct to cholescintigraphy in the evaluation of gallbladder disease, especially when visualization post morphine rules out acute cholecystitis.

  14. [Treatment of the acute diverticulitis: A systematic review].

    PubMed

    Dréanic, Johann; Sion, Elena; Dhooge, Marion; Dousset, Bertrand; Camus, Marine; Chaussade, Stanislas; Coriat, Romain

    2015-11-01

    Acute diverticulitis is a common disease with increasing incidence. In most of cases, diagnosis is made at an uncomplicated stage offering a curative attempt under medical treatment and use of antibiotics. There is a risk of diverticulitis recurrence. Uncomplicated diverticulitis is opposed to complicated forms (perforation, abscess or fistula). Recent insights in the pathophysiology of diverticulitis, the natural history, and treatments have permitted to identify new treatment strategies. For example, the use of antibiotics tends to decrease; surgery is now less invasive, percutaneous drainage is preferred, peritoneal lavage is encouraged. Treatments of the diverticulitis are constantly evolving. In this review, we remind the pathophysiology and natural history, and summarize new recommendations for the medical and surgical treatment of acute diverticulitis. PMID:26358668

  15. Pivmecillinam for the treatment of acute uncomplicated urinary infection.

    PubMed

    Nicolle, L E

    1999-12-01

    Pivmecillinam is a beta-lactam antimicrobial marketed almost two decades ago. It has been used widely for the treatment of acute cystitis in selected areas of the world, particularly in Scandinavia. With increasing resistance of community Escherichia coli isolates to trimethoprim and trimethoprim/sulphamethoxazole, as previously observed for ampicillin and sulphonamides, reassessment of empiric antimicrobial regimens for acute uncomplicated urinary infection is necessary. Thus, it is timely to revisit the role of pivmecillinam for the treatment of acute cystitis. Clinical studies document the efficacy of this antimicrobial with short course therapy for acute cystitis, and clinical practice in countries where it has been used for many years confirms its efficacy and tolerability. If this agent were more widely used for empiric treatment for acute cystitis, use of antimicrobials such as the quinolones might be avoided. Further trials to define the comparative efficacy of pivmecillinam with other antimicrobials, and further studies of community resistance in E. coli isolates to this agent are needed. PMID:10692756

  16. Temporal effects of topical morphine application on cutaneous wound healing

    PubMed Central

    Rook, Jerri M.; Hasan, Wohaib; McCarson, Kenneth E.

    2008-01-01

    Background Studies have shown that topical administration of exogenous opioid drugs impairs wound healing by inhibiting the peripheral release of neuropeptides, thereby inhibiting neurogenic inflammation. This delay is immediate and peaks during the first days of wound closure. This study examined the effects of topical morphine treatment in a cutaneous wound healing model in the rat. Methods Full-thickness 4mm diameter wounds were placed on the periscapular region of rats that subsequently received twice-daily topical applications of IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mM morphine sulfate on days 0–3 or 4–10 post-wounding or throughout the time course. Wound tissue was taken on days 1, 3, 5, 8, and 18 post-wounding and immunostained for myofibroblast and macrophage markers or stained with hematoxylin and eosin. Results Delays in wound closure observed during morphine application on days 0–3 post-wounding mimicked those seen in wounds treated with morphine throughout the entire healing process. However, no significant delays in closure were seen in wounds treated with morphine beginning on day 4 post-wounding. Treatment of wounds with morphine significantly reduced the number of myofibroblasts and macrophages in the closing wound. Additionally, morphine application resulted in decreases in skin thickness and an increase in residual scar tissue in healed skin. Conclusions These findings demonstrate the time-dependent and persistent nature of the detrimental effects of topical morphine on cutaneous wound healing. The data identify specific limitations that could be ameliorated to optimize topical opioid administration as an analgesic therapeutic strategy in the treatment of painful cutaneous wounds. PMID:18580183

  17. Ethanol Reversal of Cellular Tolerance to Morphine in Rat Locus Coeruleus Neurons

    PubMed Central

    Llorente, Javier; Withey, Sarah; Rivero, Guadalupe; Cunningham, Margaret; Cooke, Alex; Saxena, Kunal; McPherson, Jamie; Oldfield, Sue; Dewey, William L.; Bailey, Chris P.; Kelly, Eamonn; Henderson, Graeme

    2013-01-01

    Consumption of ethanol is a considerable risk factor for death in heroin overdose. We sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons, tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM). Tolerance to the opioid peptide [d-Ala2,N-MePhe4,Gly-ol]-enkephalin was not reversed by ethanol. Previous studies in LC neurons have revealed a role for protein kinase C (PKC)α in μ-opioid receptor (MOPr) desensitization by morphine and in the induction and maintenance of morphine tolerance, but we have been unable to demonstrate that 20 mM ethanol produces significant inhibition of PKCα. The ability of ethanol to reverse cellular tolerance to morphine in LC neurons was absent in the presence of the phosphatase inhibitor okadaic acid, indicating that dephosphorylation is involved. In human embryonic kidney 293 cells expressing the MOPr, ethanol reduced the level of MOPr phosphorylation induced by morphine. Ethanol reversal of tolerance did not appear to result from a direct effect on MOPr since acute exposure to ethanol (20 mM) did not modify the affinity of binding of morphine to the MOPr or the efficacy of morphine for G-protein activation as measured by guanosine 5′-O-(3-[35S]thio)triphosphate binding. Similarly, ethanol did not affect MOPr trafficking. We conclude that acute exposure to ethanol enhances the effects of morphine by reversing the processes underlying morphine cellular tolerance. PMID:23716621

  18. Effects of berberine on acquisition and reinstatement of morphine-induced conditioned place preference in mice

    PubMed Central

    Vahdati Hassani, Faezeh; Hashemzaei, Mahmoud; Akbari, Edris; Imenshahidi, Mohsen; Hosseinzadeh, Hossein

    2016-01-01

    Objective: It has been shown that berberine, a major component of Berberis vulgaris extract, modulates the activity of several neurotransmitter systems including dopamine (Da) and N-methyl-D-aspartate (NMDA) contributing to rewarding and reinforcing effects of morphine. Drug craving and relapsing even after a long time of abstinence therapy are the most important problems of addiction. In the present study, we investigated the alleviating effects of berberine on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) in mice. Materials and Methods: In male NMRI mice, the acquisition of CPP was established by 40 mg/kg of morphine sulphate injection and extinguished after the extinction training and reinstated by a 10 mg/kg injection of morphine. The effects of different doses of berberine (5, 10, and 20 mg/kg) on the acquisition and reinstatement induced by morphine were evaluated in a conditioned place preference test. Results: The results showed that intraperitoneal administration of berberine (5, 10, and 20 mg/kg) did not induce conditioned appetitive or aversive effects. Injection of berberine (10 and 20 mg/kg) 2 h before the morphine administration reduced acquisition of morphine-induced CPP. In addition, same doses of berberine significantly prevented the reinstatement of morphine-induced CPP. Conclusion: These results suggest that berberine can reduce the acquisition and reinstatement of morphine-induced conditioned place preference and may be useful in treatment of morphine addiction. PMID:27222833

  19. Effects of opioids in morphine-treated pigeons trained to discriminate among morphine, the low-efficacy agonist nalbuphine, and saline.

    PubMed

    Walker, Ellen A; Picker, Mitchell J; Granger, Arthur; Dykstra, Linda A

    2004-07-01

    In opioid-dependent subjects, the low-efficacy mu agonist nalbuphine generally precipitates withdrawal or withdrawal-like stimulus effects. To provide a more complete characterization of the discriminative stimulus effects of nalbuphine in opioid-treated subjects, seven White Carneux pigeons were treated daily with 10 mg/kg morphine i.m. and trained 6 h later to discriminate among 10 mg/kg morphine, 1.0 mg/kg nalbuphine, and saline by responding on one of three different keys. When tested, morphine produced morphine-key responding and nalbuphine produced nalbuphine-key responding. Replacing the daily morphine injection with saline produced nalbuphine-key responding, and this effect was reversed by the administration of morphine. In substitution tests with other compounds, the antagonists naltrexone (i.m.) and CTAP (D-Phe-Cys-Tyr-D-Tryp-Lys-Thr-Pen-Thr-NH2) (i.c.v.) produced nalbuphine-key responding. High-efficacy agonists fentanyl and etorphine produced morphine-key responding. The intermediate-efficacy agonists buprenorphine, dezocine, and butorphanol produced a pattern of morphine-, saline-, and/or nalbuphine-key responding that differed across individual pigeons. The lower efficacy agonists nalorphine and levallorphan produced predominantly nalbuphine-key responding. The kappa agonists spiradoline and U50,488 [trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide methanesulfonate], the nonopioid d-amphetamine, and saline produced predominantly saline-key responding. Naltrexone and nalbuphine dose dependently reversed the morphine-key responding produced by the training dose of morphine. Together, these data suggest that the discriminative-stimulus effects of the low-efficacy micro agonist nalbuphine in morphine-treated pigeons are similar to those of other low-efficacy agonists, naltrexone, and the termination of daily morphine treatment. PMID:15044559

  20. Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats

    SciTech Connect

    Fuhrman-Lane, C.; Fujimoto, J.M.

    1982-09-01

    The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

  1. Pulmonary function after treatment for acute lymphoblastic leukaemia in childhood.

    PubMed Central

    Nysom, K.; Holm, K.; Olsen, J. H.; Hertz, H.; Hesse, B.

    1998-01-01

    The aim of this study was to examine pulmonary function after acute lymphoblastic leukaemia in childhood and identify risk factors for reduced pulmonary function. We studied a population-based cohort of 94 survivors of acute lymphoblastic leukaemia in childhood who were in first remission after treatment without spinal irradiation or bone marrow transplantation. Pulmonary function test results were compared with reference values for our laboratory, based on 348 healthy subjects who had never smoked from a local population study. A median of 8 years after cessation of therapy (range 1-18 years) the participants had a slight, subclinical, restrictive ventilatory insufficiency and reduced transfer factor and transfer coefficient. The changes in lung function were related to younger age at treatment and to more dose-intensive treatment protocols that specified more use of cranial irradiation and higher cumulative doses of anthracyclines, cytosine arabinoside and intravenous cyclophosphamide than previous protocols. We conclude that, 8 years after treatment without bone marrow transplantation or spinal irradiation, survivors of childhood acute lymphoblastic leukaemia in first remission were without pulmonary symptoms but had signs of slight restrictive pulmonary disease including reduced transfer factor. The increased dose intensity of many recent protocols for childhood acute lymphoblastic leukaemia may lead to increased late pulmonary toxicity. PMID:9662245

  2. Epidemiology and Treatment of Acute Promyelocytic Leukemia in Latin America

    PubMed Central

    Rego, E.M.; Jácomo, R.H.

    2011-01-01

    Distinct epidemiological characteristics have been described in Acute Promielocytic Leukemia (APL). Populations from Latin America have a higher incidence of APL and in some geographic areas a distinct distribution of the PML-RARA isoforms is present. Here, we review the main differences in APL epidemilogy in Latin America as well as treatment outcomes. PMID:22110899

  3. Treatment strategies for acute metabolic disorders in neonates

    PubMed Central

    Mohamed, Sarar

    2011-01-01

    Acute metabolic emergencies in neonates represent a challenge to the medical and nursing staff. If not treated optimally, these disorders are associated with poor outcome. Early diagnosis, supportive therapy and specific measures addressing the derranged metabolic process are the gold standards for favorable results. This review highlights treatment strategies for Inborn Errors of Metabolism (IEM) presenting in the neonatal period.

  4. The analgesic effect of combined treatment with intranasal S-ketamine and intranasal midazolam compared with morphine patient-controlled analgesia in spinal surgery patients: a pilot study

    PubMed Central

    Riediger, Christine; Haschke, Manuel; Bitter, Christoph; Fabbro, Thomas; Schaeren, Stefan; Urwyler, Albert; Ruppen, Wilhelm

    2015-01-01

    Objectives Ketamine is a well-known analgesic and dose-dependent anesthetic used in emergency and disaster medicine. Recently, a new formulation of S-ketamine, as an intranasal spray, was developed and tested in our institution in healthy volunteers. The authors investigated the effect of intranasal S-ketamine spray combined with midazolam intranasal spray in postoperative spinal surgery patients. Materials and methods In this prospective, computer-randomized, double-blinded noninferiority study in spinal surgery patients, the effects of intranasal S-ketamine and midazolam were compared with standard morphine patient-controlled analgesia (PCA). The primary end point was the numeric rating scale pain score 24 hours after surgery. Results Twenty-two patients finished this study, eleven in each group. There were similar numeric rating scale scores in the morphine PCA and the S-ketamine-PCA groups at 1, 2, 4, 24, 48, and 72 hours after surgery during rest as well as in motion. There were no differences in the satisfaction scores at any time between the groups. The number of bolus demands and deliveries was not significantly different. Discussion In our study, we found that an S-ketamine intranasal spray combined with intra-nasal midazolam was similar in effectiveness, satisfaction, number of demands/deliveries of S-ketamine and morphine, and number/severity of adverse events compared with standard intravenous PCA with morphine. S-ketamine can be regarded as an effective alternative for a traditional intravenous morphine PCA in the postoperative setting. PMID:25709497

  5. Treatment of acute bronchospasm in elderly patients.

    PubMed

    Berger, William E

    2005-12-01

    Both asthma and chronic obstructive pulmonary disease (COPD) are often underdiagnosed and undertreated among the elderly. Patient compliance with treatments plans and medication schedules are often less than ideal. This paper presents results from clinical studies examining levalbuterol and racemic albuterol use among elderly patients who have asthma or COPD. PMID:19667714

  6. Endovascular Treatment of Acute Thrombosis of Cerebral Veins and Sinuses

    PubMed Central

    Yakovlev, Sergey Borisovich; Bocharov, Aleksei Vasilievich; Mikeladze, Ketevan; Gasparian, Sergey Surenovich; Serova, Natalia Konstantinovna; Shakhnovich, Alexander Romanovich

    2014-01-01

    Summary Acute thrombosis of cerebral veins and sinuses (ATCVS) is a multifactorial disease with grave consequences. Because of its rare occurrence there are no proven treatment guidelines. Sixteen patients with ATCVS were treated. The final diagnosis was confirmed by digital subtraction angiography. Sinus catheterization was performed via transfemoral venous access. Treatment included mechanical manipulation of thrombi and thrombolytic therapy. A regression of clinical symptoms with a concomitant decrease of intracranial hypertension was achieved in all patients. Long-term results were studied in eight patients: none presented clinical signs of intracranial hypertension. Endovascular transvenous recanalization is an effective treatment for acute thrombosis of cerebral veins and sinuses. Along with the local thrombolysis, significant potential in the treatment of this complex pathology lies in the transvenous endovascular techniques of mechanical thrombus extraction, especially in patients with intracranial hemorrhage for whom the use of thrombolytic agents is restricted. PMID:25196622

  7. Acute behavioral interventions and outpatient treatment strategies with suicidal adolescents

    PubMed Central

    O’Brien, Kimberly H. McManama; Singer, Jonathan B.; LeCloux, Mary; Duarté-Vélez, Yovanska; Spirito, Anthony

    2015-01-01

    Despite the prevalence of suicidal thoughts and behaviors among adolescents, there is limited knowledge of effective interventions to use with this population. This paper reviews the findings of studies on behavioral interventions for adolescents who are at acute suicide risk, as well as outpatient treatment and risk management strategies with suicidal adolescents. The importance of addressing comorbid behaviors and enhancing protective factors are discussed. Cultural considerations in working with suicidal adolescents and strategies for conducting culturally competent treatment are explored. PMID:26279646

  8. Acute treatment of anaphylaxis in children

    PubMed Central

    Goldman, Ran D.

    2013-01-01

    Abstract Question A 3-year-old was rushed to my office after eating a friend’s chocolate bar that contained nuts. He immediately developed urticaria on his face and swelling of his lips, and he had a persistent cough. What is the best treatment for a child with anaphylaxis? Should this family receive a prescription for an epinephrine autoinjector device? Answer Intramuscular epinephrine injection is a safe and effective treatment of anaphylaxis in children. Children with systemic allergic reactions should carry epinephrine autoinjectors at all times, and should certainly have one with them at school. In order for epinephrine autoinjectors to be effective, children and their families need to be educated on how to properly use the devices, as well as keep in mind the product’s expiration date. PMID:23851537

  9. Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome

    PubMed Central

    Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

    2014-01-01

    Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress. PMID:24932421

  10. Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome.

    PubMed

    Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

    2013-09-18

    Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress. PMID:24932421

  11. Minimally Invasive Surgical Treatment of Acute Epidural Hematoma: Case Series

    PubMed Central

    2016-01-01

    Background and Objective. Although minimally invasive surgical treatment of acute epidural hematoma attracts increasing attention, no generalized indications for the surgery have been adopted. This study aimed to evaluate the effects of minimally invasive surgery in acute epidural hematoma with various hematoma volumes. Methods. Minimally invasive puncture and aspiration surgery were performed in 59 cases of acute epidural hematoma with various hematoma volumes (13–145 mL); postoperative follow-up was 3 months. Clinical data, including surgical trauma, surgery time, complications, and outcome of hematoma drainage, recovery, and Barthel index scores, were assessed, as well as treatment outcome. Results. Surgical trauma was minimal and surgery time was short (10–20 minutes); no anesthesia accidents or surgical complications occurred. Two patients died. Drainage was completed within 7 days in the remaining 57 cases. Barthel index scores of ADL were ≤40 (n = 1), 41–60 (n = 1), and >60 (n = 55); scores of 100 were obtained in 48 cases, with no dysfunctions. Conclusion. Satisfactory results can be achieved with minimally invasive surgery in treating acute epidural hematoma with hematoma volumes ranging from 13 to 145 mL. For patients with hematoma volume >50 mL and even cerebral herniation, flexible application of minimally invasive surgery would help improve treatment efficacy. PMID:27144170

  12. Treatment of Acute Promyelocytic Leukemia for Older Patients

    PubMed Central

    Prebet, Thomas; Gore, Steven D.

    2013-01-01

    Acute promyelocytic leukemia (APL) represents a remarkable disease in which leukemogenesis is driven by the PML-RARα oncogene and for which targeted treatment with all-trans retinoic acid (ATRA)–based therapy allows substantial chance of cure. APL is seen in a small subset of older patients, with age representing one of the most important prognostic factors for outcome of treatment. Unlike other acute leukemias, the inferior outcomes for APL in older patients relates less to changes in disease biology and more to increased toxicity of ATRA and chemotherapy combination regimens used to induce hematologic and molecular responses. Risk-adapted strategies that use less-toxic agents, such as arsenic trioxide, allow treatment of older patients, with greater efficiency and better chances of cure. PMID:21393443

  13. Intra-Arterial Treatment Methods in Acute Stroke Therapy

    PubMed Central

    Nguyen, Thanh N.; Babikian, Viken L.; Romero, Rafael; Pikula, Aleksandra; Kase, Carlos S.; Jovin, Tudor G.; Norbash, Alexander M.

    2011-01-01

    Acute revascularization is associated with improved outcomes in ischemic stroke patients. It is unclear which method of intra-arterial intervention, if any, is ideal. Promising approaches in acute stroke treatment are likely a combination of intravenous and endovascular revascularization efforts, combining early treatment initiation with direct clot manipulation and/or PTA/stenting. In this review, we will discuss available thrombolytic therapies and endovascular recanalization techniques, beginning with chemical thrombolytic agents, followed by mechanical devices, and a review of ongoing trials. Further randomized studies comparing medical therapy, intravenous and endovascular treatments are essential, and their implementation will require the wide support and enthusiasm from the neurologic, neuroradiologic, and neurosurgical stroke communities. PMID:21516256

  14. Potentiation of morphine analgesia by subanesthetic doses of pentobarbital.

    PubMed

    Pontani, R B; Vadlamani, N L; Misra, A L

    1985-03-01

    Pentobarbital pretreatment reportedly either inhibits, enhances or has no effect on morphine analgesia. The effect of subanesthetic doses of sodium pentobarbital (8-12 mg kg-1, SC) delivered via a delivery system on analgesia of morphine (5 mg kg-1, SC or 1 mg kg-1, IV) acutely administered 45 min after the sodium pentobarbital pellet implantation was assessed using the warm water (55 degrees C)-induced tail-withdrawal reflex in male Wistar rats. Significant potentiation of morphine analgesia was observed in sodium pentobarbital as compared to the placebo-pelleted animals. Pharmacokinetic or dispositional factors were not involved in this potentiation, which was possibly due to the activation of the descending inhibitory control pathways of nociceptive spinal tail-withdrawal reflex by a combined interaction of two drugs at spinal and supraspinal sites of action, that mediate opiate antinociception. PMID:3991755

  15. The acute and preventative treatment of episodic migraine

    PubMed Central

    Miller, Sarah

    2012-01-01

    Episodic migraine is a common debilitating condition with significant worldwide impact. An effective management plan must include acute treatment to relieve the pain and potential disability associated with the attacks and may also include preventative treatments with an aim of decreasing attack frequency and severity in the longer term. Acute treatments must be limited to a maximum of 2-3 days a week to prevent medication overuse headache and focus on simple analgesia, non-steroidal anti-inflammatory drugs and triptans. Preventative treatments are numerous and should be considered when migraine attacks are frequent and or disabling, acute medication is failing, in special circumstances such as hemiplegic migraines or if the patient requests them. All preventative medications must be given at therapeutic doses for at least 6-8 weeks before an adequate trial can be judged ineffective. The most important factor in choosing drugs is the patient and the clinical features of their attack and treatment should be tailored to these. Relative co-morbidities will influence drug choice, as will the side effect profile and the efficacy of the drug. First line preventative drugs include ß-blockers, amitriptyline and anti-epileptic drugs such as topiramate and valproate. Drugs with lower efficacy or poorer side effect profiles include selective serotonin reuptake inhibitors (SSRIs), calcium channel antagonists, gabapentin and herbal medicines. PMID:23024562

  16. Attenuation of morphine tolerance by minocycline and pentoxifylline in naive and neuropathic mice.

    PubMed

    Mika, Joanna; Wawrzczak-Bargiela, Agnieszka; Osikowicz, Maria; Makuch, Wioletta; Przewlocka, Barbara

    2009-01-01

    We have previously demonstrated that glial inhibitors reduce the development of allodynia and hyperalgesia, potentiating the effect of a single morphine dose in a neuropathic pain model. This study explores the effects of two glial activation inhibitors, minocycline and pentoxifylline, on the development of tolerance to morphine in naive and chronic constriction injury (CCI)-exposed mice. Administration of morphine to naive (20 mg/kg; i.p.) and CCI-exposed mice (40 mg/kg; i.p.) twice daily resulted in tolerance to its anti-nociceptive effect after 6 days. Injections of morphine were combined with minocycline (30 mg/kg, i.p.) or pentoxifylline (20 mg/kg, i.p.) administered as two preemptive doses before first morphine administration in naive or pre-injury in CCI-exposed mice, and repeated twice daily 30 min before each morphine administration. With treatment, development of morphine tolerance was delayed by 5 days (from 6 to 11 days), as measured by the tail-flick test in naive and by tail-flick, von Frey, and cold plate tests in CCI-exposed mice. Western blot analysis of CD11b/c and GFAP protein demonstrated that minocycline and pentoxifylline, at doses delaying development of tolerance to morphine analgesia, significantly diminished the morphine-induced increase in CD11b/c protein level. We found that repeated systemic administration of glial inhibitors significantly delays development of morphine tolerance by attenuating the level of this microglial marker under normal and neuropathic pain conditions. Our results support the idea that targeting microglial activation during morphine therapy/treatment is a novel and clinically promising method for enhancing morphine's analgesic effects, especially in neuropathic pain. PMID:18684397

  17. Acute low back pain: diagnostics and treatment.

    PubMed

    Becker, F C

    2001-03-01

    How many times have you heard from a patient or groaned yourself "Oh, my aching back?" Innocuous movements such as reaching, stooping, or leaning are halted mid-performance as you sense "something" give, catch, snap, grab, or slide in your lower back. Such subjective complaints may also include sensations of discomfort described as stabbing, sharp, dull, hot/burning, tingling, or numbing. In practice, you will be required to assess these subjective symptoms, effectively document objective data, formulate a diagnosis, and plan appropriate treatment for your patients. Careful attention to history, associated symptoms, and following a systematic approach to back pain can make the rule-in/out differentials less taxing on both the practitioner and the patient. PMID:11329554

  18. The interaction of adenosine and morphine on pentylenetetrazole-induced seizure threshold in mice.

    PubMed

    Moezi, Leila; Akbarian, Reyhane; Niknahad, Hossein; Shafaroodi, Hamed

    2013-09-01

    Adenosine agonists or low doses of morphine exert anti-convulsant effects in different models of seizures. On the other hand, a tight interaction has been reported between morphine and adenosine in various paradigms. This study investigated the effect of the interaction of adenosine and morphine on seizure susceptibility in the intravenous mouse model of pentylenetetrazole (PTZ)-induced clonic seizures. The researchers used acute systemic administration of morphine, N(6)-cyclohexyladenosine (CHA) (a selective A1 receptor agonist), naltrexone (an opioid receptor antagonist) and 8-Cyclopentyl-1,3-dimethylxanthine (8-CPT) (a selective A1 receptor antagonist). Acute administration of morphine (0.25, 0.5 and 1 mg/kg) or CHA (0.25, 0.5, 1, 2 and 4 mg/kg) raised the threshold of seizures induced by PTZ. Non-effective dose of 8-CPT (2 mg/kg) inhibited the anticonvulsant effects of CHA (0.5 and 1 mg/kg). Combination of sub-effective doses of morphine (0.125 mg/kg) and CHA (0.125 mg/kg) increased clonic seizure latency showing the additive effect of morphine and CHA. The enhanced latency induced by combination of low doses of morphine and CHA completely reversed by 8-CPT (2 mg/kg) or naltrexone (1 mg/kg). Moreover, 8-CPT (2 mg/kg) inhibited anticonvulsant effects of morphine (0.25 and 0.5 mg/kg) and naltrexone (1 mg/kg) inhibited anticonvulsant effects of CHA (0.25, 0.5 and 1 mg/kg). Combination of low doses of 8-CPT (1 mg/kg) and naltrexone (0.5 mg/kg) inhibited the anticonvulsant effect of CHA (0.5 and 1 mg/kg). In conclusion, adenosine and morphine exhibit an additive effect on the enhancement of the pentylenetetrazole-induced seizure threshold in mice, probably through A1 or μ receptors. PMID:23624288

  19. [Tulozin in combined treatment of patients with acute urinary retention].

    PubMed

    Avdoshin, V P; Andriukhin, M I; Mikhaĭlikov, T G; Ol'shanskaia, E V; Khunov, A Z

    2009-01-01

    There is much evidence that tulozin promotes recovery of spontaneous urination, Qmax and is effective in combined treatment of patients with acute retention of urine caused by prostatic adenoma. Tulozin produces positive changes in the lower urinary tract symptoms. Rare occurrence of side effects enables long-term treatment and achievement of good therapeutic response. Tulozin is recommended for patients of younger age, with minimal comorbid pathology, hypotonic with orthostatic reactions, history of side effects in the treatment of other alpha-adrenoblockers, in comorbid hypertention, hypercholesterolemia, retrograde ejaculation, low potention, overactive bladder, prostatitis, after prostatic TUR, transvesical adenomectomy. PMID:19824378

  20. Re-evaluating the treatment of acute optic neuritis

    PubMed Central

    Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

    2015-01-01

    Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis. Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite ‘normal’ (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury. In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration. In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. PMID:25355373

  1. Re-evaluating the treatment of acute optic neuritis.

    PubMed

    Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

    2015-07-01

    Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite 'normal' (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury.In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration.In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. PMID:25355373

  2. Role of calcium in morphine dependence and naloxone-precipitated withdrawal in mice

    PubMed Central

    Seth, Vikas; Upadhyaya, Prerna; Moghe, Vijay; Ahmad, Mushtaq

    2011-01-01

    Purpose To explore the role of calcium in morphine withdrawal syndrome using various agents affecting calcium levels in cytoplasm. Methods Mice were rendered dependent on morphine by subcutaneous injection of morphine, and withdrawal was induced 4 hours later by injecting the opioid antagonist, naloxone. Mice were observed for 30 minutes for signs of withdrawal, ie, characteristic jumping, hyperactivity, urination, and diarrhea. Various calcium channel blockers were injected intraperitoneally 30 minutes before naloxone to evaluate their influence on the severity of the withdrawal syndrome. We also tested the effect of combination levodopa-carbidopa pretreatment and its interaction with a selective alpha-1 blocker, terazosin, on naloxone-precipitated withdrawal in mice acutely dependent on morphine. Results A significant dose-dependent attenuation of naloxone-induced morphine withdrawal syndrome was observed with calcium channel blockers, ie, verapamil 20 mg/kg (P < 0.05) and diltiazem 30 mg/kg (P < 0.01). Combination levodopa-carbidopa pretreatment facilitated the morphine withdrawal syndrome, and this was found to be blocked by terazosin, although not to a statistically significant (P > 0.05) extent. Conclusion The results indicate that calcium plays an important role in the genesis of morphine dependence and withdrawal, and suggest the usefulness of calcium channel blockers in the management of morphine withdrawal syndrome.

  3. Rifaximin for the treatment of acute infectious diarrhea.

    PubMed

    Hong, Kyoung Sup; Kim, Joo Sung

    2011-07-01

    Rifaximin is a nonabsorbable rifamycin derivative with an excellent safety profile and a broad spectrum of antimicrobial activity against a variety of enteropathogens causing acute infectious diarrhea. After oral ingestion, its bioavailability is known to be less than 0.4%, and it has a low potential for significant drug interactions. In the treatment of travelers' diarrhea caused by noninvasive diarrheagenic Escherichia coli, it has been demonstrated that rifaximin significantly shortens the duration of diarrhea and has an efficacy similar to that of ciprofloxacin. Moreover, according to two randomized placebo-controlled trials, prophylactic treatment with rifaximin reduced the risk of developing travelers' diarrhea by more than 50% compared with the placebo group. For the treatment of acute diarrhea unrelated to travel, a short course of rifaximin significantly reduced the duration of diarrhea, and its overall efficacy was comparable to that of ciprofloxacin. The discrepancy between the in vitro and in vivoantimicrobial activities of rifaximin, however, and the clinical implication of the rapid appearance of bacterial resistance, must be further elucidated. In conclusion, this gut-selective antibiotic seems to be a promising option for the treatment of acute infectious diarrhea secondary to noninvasive E. coli and also appears to be effective in chemoprophylaxis for travelers' diarrhea. PMID:21765867

  4. Rifaximin for the treatment of acute infectious diarrhea

    PubMed Central

    Hong, Kyoung Sup; Kim, Joo Sung

    2011-01-01

    Rifaximin is a nonabsorbable rifamycin derivative with an excellent safety profile and a broad spectrum of antimicrobial activity against a variety of enteropathogens causing acute infectious diarrhea. After oral ingestion, its bioavailability is known to be less than 0.4%, and it has a low potential for significant drug interactions. In the treatment of travelers’ diarrhea caused by noninvasive diarrheagenic Escherichia coli, it has been demonstrated that rifaximin significantly shortens the duration of diarrhea and has an efficacy similar to that of ciprofloxacin. Moreover, according to two randomized placebo-controlled trials, prophylactic treatment with rifaximin reduced the risk of developing travelers’ diarrhea by more than 50% compared with the placebo group. For the treatment of acute diarrhea unrelated to travel, a short course of rifaximin significantly reduced the duration of diarrhea, and its overall efficacy was comparable to that of ciprofloxacin. The discrepancy between the in vitro and in vivoantimicrobial activities of rifaximin, however, and the clinical implication of the rapid appearance of bacterial resistance, must be further elucidated. In conclusion, this gut-selective antibiotic seems to be a promising option for the treatment of acute infectious diarrhea secondary to noninvasive E. coli and also appears to be effective in chemoprophylaxis for travelers’ diarrhea. PMID:21765867

  5. [Opium (heroin * morphine)].

    PubMed

    Hiramatsu, Masayuki

    2010-08-01

    The number of people dependent on opiate drugs, including heroin, is still high, and these abused drugs are major social issues, both in the social science and medically. The mechanisms of physical dependence and withdrawal symptoms in laboratory animals are becoming clear; however, no useful method to detoxify abusers with opioid dependence in clinical situation has been established, and alternative therapy with methadone, used in Europe and America, cannot be used in Japan. Here, I will outline the global trend of opium abuse, including heroin and morphine, and summarize the problems of heroin abuse. PMID:20715484

  6. SWIM (sickle with ibuprofen and morphine) randomised controlled trial fails to recruit: lessons learnt

    PubMed Central

    Cho, Gavin; Anie, Kofi A; Buckton, Jacky; Kiilu, Patricia; Layton, Mark; Alexander, Lydia; Hemmaway, Claire; Sutton, Dorothy; Amos, Claire; Doré, Caroline J; Kahan, Brennan; Meredith, Sarah

    2016-01-01

    Objectives Sickle With Ibuprofen and Morphine (SWIM) trial was designed to assess whether co-administration of ibuprofen (a non-steroidal anti-inflammatory drug) resulted in a reduction of opioid consumption delivered by patient-controlled analgesia (PCA) for acute pain in sickle cell disease. Design A randomised, placebo-controlled, double-blind trial. Setting UK multicentre trial in acute hospital setting. Participants Adults with sickle cell disease of any gender and phenotype aged 16 years and over. Interventions Oral ibuprofen at a dose of 800 mg three times daily or placebo in addition to opioids (morphine or diamorphine) administered via PCA pump for up to 4 days. Main outcome measures The primary outcome measure was opioid consumption over 4 days following randomisation. Results The SWIM trial closed early because it failed to randomise to its target of 316 patients within a reasonable time. Conclusions The key issues identified include the unanticipated length of time between informed consent and randomisation, difficulties in randomisation of patients in busy emergency departments, availability of trained staff at weekends and out of hours, fewer centres than expected using PCA routinely for sickle cell pain treatment, lack of research staff and support for participation, and the trial design. There are implications for future UK trials in sickle cell disease. Trial registration number ISRCTN97241637, NCT00880373; Pre-results. PMID:27288381

  7. Effects of Estrogen Receptor Modulators on Morphine Induced Sensitization in Mice Memory

    PubMed Central

    Anoush, Mahdieh; Jani, Ali; Sahebgharani, Moosa; Jafari, Mohammad Reza

    2015-01-01

    Objective: In this study, the effects of estradiol valerate and raloxifenea selective estrogen receptor modulator; (SERM) on morphine induced sensitization were examined in mice memory, according to the step-down passive avoidance task. Method: The mice received morphine or estradiol and raloxifene for three days alone or in combination with morphine. After a drug free period of 5 days, the subjects received saline or morphine as pre- training treatments followed by a pre-test saline administration. The memory retrieval was evaluated using step-down passive avoidance test both on the training and test day. Results: The results illustrated that the three- day administration of morphine induced sensitization through the enhancement of memory retrieval (morphine induced sensitization in mice memory). Both the three- day administration of estradiol valerate alone and with morphine (5 mg/kg) restored memory. On the other hand, the three- day administration of raloxifene had no effect on memory retrieval alone, but declined morphine induced sensitization in mice memory. Conclusion: The results of the study indicated that there is an interaction between estrogen receptor modulators and morphine induced sensitization in mice memory. PMID:26877753

  8. Idiopathic thrombocytopenic purpura following successful treatment of acute lymphoblastic leukemia.

    PubMed

    Tannir, N M; Kantarjian, H

    2001-03-01

    Thrombocytopenia is common in patients with acute lymphocytic leukemia (ALL) at diagnosis. It is a universal side effect of dose-intensive regimens employed in the treatment of adult ALL. In patients with ALL who achieve remission, thrombocytopenia frequently indicates relapse. We report three adult patients successfully treated for ALL who developed thrombocytopenia and were found to have immune-mediated thrombocytopenia (ITP). Possible pathophysiologic mechanisms underlying the association of ALL and ITP are discussed. PMID:11342378

  9. Acute pancreatitis as a complication of childhood cancer treatment.

    PubMed

    Stefanović, Milica; Jazbec, Janez; Lindgren, Fredrik; Bulajić, Milutin; Löhr, Matthias

    2016-05-01

    Acute pancreatitis (AP) is now well recognized as a possible complication of childhood cancer treatment, interrupting the chemotherapy regimen, and requiring prolonged hospitalization, possibly with intensive care and surgical intervention, thereby compromising the effect of chemotherapy and the remission of the underlying malignant disease. This review summarizes the current literature and presents the various etiological factors for AP during chemotherapy as well as modern trends in the diagnosis and therapy of AP in children. PMID:26872431

  10. Inhibition of Morphine Tolerance and Dependence by the NMDA Receptor Antagonist MK-801

    NASA Astrophysics Data System (ADS)

    Trujillo, Keith A.; Akil, Huda

    1991-01-01

    The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.

  11. Long-term stability of morphine hydrochloride in 0.9% NaCl infusion polyolefin bags after freeze-thaw treatment and in polypropylene syringes at 5 degrees C + 3 degrees C.

    PubMed

    Hecq, J-D; Godet, M; Gillet, P; Jamart, J; Galanti, L

    2014-01-01

    The aim of this study was to investigate the long-term stability of morphine hydrochloride in 0.9% NaCI infusion polyolefin bags and polypropylene syringes after storage at 5 degrees C + 3 degrees C and to evaluate the influence of initial freezing and microwave thawing on this stability. Ten polyolefin bags and five polypropylene syringes containing 100 mL of 1 mg/mL of morphine hydrochloride solution in 0.9% NaCI were prepared under aseptic conditions. Five polyolefin bags were frozen at -20 degrees C for 90 days before storage. Immediately after the preparation and after thawing, 2 mL of each bag were withdrawn for the initial concentration measurements. All polyolefin bags and polypropylene syringes were then refrigerated at 5 degrees C + 3 degrees C for 58 days during which the morphine concentrations were measured periodically by high-performance liquid chromatography using a reversed-phase column, naloxone as internal standard, a mobile phase consisting of 5% acetonitrile and 95% of KH2PO4 buffer (pH 3.50), and detection with diode array detector at 254 nm. Visual and microscopic observations and spectrophotometric and pH measurements were also performed. Solutions were considered stable if the concentration remained superior to 90% of the initial concentration. The degradation products peaks were not quantitatively significant and were resolved from the native drug. Polyolefin bag and polypropylene syringe solutions were stable when stored at 5 degrees C + 3 degrees C during these 58 days. No color change or precipitation in the solutions was observed. The physical stability was confirmed by visual, microscopic, and spectrophotometric inspection. There was no significant change in pH during storage. Freezing and microwave thawing didn't influence the infusion stability. Morphine hydrochloride infusions may be prepared in advance by centralized intravenous additive service, frozen in polyolefin bags, and microwave thawed before storage under refrigeration

  12. Acute and long-term treatment of mania.

    PubMed

    Vieta, Eduard; Sanchez-Moreno, Jose

    2008-01-01

    The treatment of mania starts with a correct diagnosis and elementary measures to prevent risks for the patient, relatives, and others. Sometimes, compulsory admission and treatment may be required for a few days. Patients with psychotic or mixed mania may be more difficult to treat. At the present time, there is solid evidence supporting the use of lithium, the anticonvulsants valproate and carbamazepine, and the antipsychotics chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment-refractory cases. However, in clinical practice, combination therapy is the rule rather than the exception. The treatment of acute mania deserves a long-term view, and the evidence base for some treatments may be stronger than for others. When taking decisions about treatment, tolerability should also be a major concern, as differences in safety and tolerability may exceed differences in efficacy for most compounds. Psychoeducation of patients and caregivers is a powerful tool that should be used in combination with medication for optimal long-term outcome. Functional recovery should be the ultimate goal. PMID:18689287

  13. Acute Infection in Total Knee Arthroplasty: Diagnosis and Treatment

    PubMed Central

    Martínez-Pastor, Juan Carlos; Maculé-Beneyto, Francisco; Suso-Vergara, Santiago

    2013-01-01

    Infection is one of the most serious complications after total knee arthroplasty (TKA). The current incidence of prosthetic knee infection is 1-3%, depending on the series. For treatment and control to be more cost effective, multidisciplinary groups made up of professionals from different specialities who can work together to eradicate these kinds of infections need to be assembled. About the microbiology, Staphylococcus aureus and coagulase-negative staphylococcus were among the most frequent microorganisms involved (74%). Anamnesis and clinical examination are of primary importance in order to determine whether the problem may point to a possible acute septic complication. The first diagnosis may then be supported by increased CRP and ESR levels. The surgical treatment for a chronic prosthetic knee infection has been perfectly defined and standardized, and consists in a two-stage implant revision process. In contrast, the treatment for acute prosthetic knee infection is currently under debate. Considering the different surgical techniques that already exist, surgical debridement with conservation of the prosthesis and polythene revision appears to be an attractive option for both surgeon and patient, as it is less aggressive than the two-stage revision process and has lower initial costs. The different results obtained from this technique, along with prognosis factors and conclusions to keep in mind when it is indicated for an acute prosthetic infection, whether post-operative or haematogenous, will be analysed by the authors. PMID:23919094

  14. Acute diverticulitis. Comparison of treatment in immunocompromised and nonimmunocompromised patients.

    PubMed

    Perkins, J D; Shield, C F; Chang, F C; Farha, G J

    1984-12-01

    The clinical course and required treatment of diverticulitis were reviewed in 76 nonimmunocompromised patients and 10 immunocompromised patients. The immunocompromised patients presented with either minimal or no symptoms and findings. Therefore, to make the diagnosis of acute diverticulitis in this group, a high index of suspicion must be maintained. The required treatment varied considerably between the two groups. In 45 nonimmunocompromised patients (76 percent), medical therapy was successful. Medical treatment failed in the other 14 patients (24 percent). However, the compromised group had no patients in whom medical therapy was successful (100 percent failure rate). Thirty-one of the nonimmunocompromised patients (41 percent) required an operation, whereas 100 percent of the immunocompromised patients with acute diverticulitis required an operation. By relating postoperative complications, we were unable to determine the initial operative procedure of choice in the nonimmunocompromised group; however, in the immunocompromised group, colostomy and resection had fewer surgical complications than colostomy and drainage. The immunocompromised patient with acute diverticulitis requires operation. We believe the operation of choice is colostomy and resection of the involved segment. PMID:6507744

  15. Oral almotriptan: practical uses in the acute treatment of migraine.

    PubMed

    Dowson, Andrew J

    2004-05-01

    Almotriptan (Almogran, Lundbeck; Almirall Prodesfarma; Axert, Ortho-McNeil) is a novel 5-HT(1B/1D) receptor agonist (triptan) that is widely available on prescription for the acute treatment of migraine. Almotriptan has pharmacodynamic and pharmacokinetic profiles that make it suitable for use in this indication. It is a potent agonist at 5-HT(1B), (1D) and (1F) receptors, while having a low affinity for other 5-HT receptors. It is also a potent inhibitor of neurogenic inflammation. Almotriptan has a high oral bioavailability, is absorbed rapidly, has a relatively short plasma half-life and its route of elimination presents few potential problems. Placebo-controlled dose-finding studies have demonstrated that almotriptan tablets are effective and well-tolerated in the acute treatment of migraine, with a 12.5 mg dose providing the best balance between efficacy and tolerability. Large placebo-controlled studies show that the efficacy of oral almotriptan is comparable with that of the other oral triptans. In direct comparator-controlled studies, almotriptan was as effective as sumatriptan 50 and 100 mg but had a superior tolerability profile. Furthermore, the efficacy and tolerability of almotriptan is sustained in the long term following open-label administration. Meta-analyses and post hoc analyses of clinical data confirm these findings. In conclusion, almotriptan 12.5 mg is a good therapeutic choice for the symptomatic treatment of acute migraine attacks. PMID:15853532

  16. 18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats.

    PubMed

    Glick, S D; Kuehne, M E; Maisonneuve, I M; Bandarage, U K; Molinari, H H

    1996-05-01

    Ibogaine, a naturally occurring iboga alkaloid, has been claimed to be effective in treating addiction to opioids and stimulants, and has been reported to inhibit morphine and cocaine self-administration in rats. However, ibogaine also has acute nonspecific side effects (e.g. tremors, decreased motivated behavior in general) as well as neurotoxic effects (Purkinje cell loss) manifested in the vermis of the cerebellum. 18-Methoxycoronaridine (MC) is a novel, synthetic iboga alkaloid congener that mimics ibogaine's effects on drug self-administration without appearing to have ibogaine's other adverse effects. Acutely, in rats, MC decreased morphine and cocaine self-administration but did not affect bar-press responding for water. In some rats, treatment with MC (40 mg/kg) induced prolonged decreases in morphine or cocaine intake lasting several days or weeks. MC had no apparent tremorigenic effect, and there was no evidence of cerebellar toxicity after a high dose (100 mg/kg) of MC. Similar to the effects of ibogaine and other iboga alkaloids that inhibit drug self-administration, MC (40 mg/kg) decreased extracellular levels of dopamine in the nucleus accumbens. MC therefore appears to be a safer, ibogaine-like agent that might be useful in the treatment of addictive disorders. PMID:8782860

  17. The selective mGlu2/3 receptor agonist LY354740 attenuates morphine-withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal.

    PubMed

    Vandergriff, J; Rasmussen, K

    1999-02-01

    Naltrexone-precipitated morphine withdrawal induces hyperactivity of locus coeruleus (LC) neurons, as well as a plethora of behavioral withdrawal signs. Previous research has demonstrated that an increased release of glutamate and activation of AMPA receptors, particularly in the LC, play an important role in opiate withdrawal. LY354740 is a novel Group II metabotropic glutamate mGlu2/3 receptor agonist that decreases the release of glutamate. Therefore, we investigated the effect of LY354740 on naltrexone-precipitated morphine-withdrawal-induced activation of LC neurons and behavioral signs of morphine withdrawal. In in vivo recordings from anesthetized rats, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently attenuated the morphine-withdrawal-induced activation of LC neurons. In unanesthetized, morphine-dependent animals, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently suppressed the severity and occurrence of many naltrexone-precipitated morphine-withdrawal signs. These results indicate mGlu2/3 receptor agonists: (1) can attenuate the morphine-withdrawal-induced activation of LC neurons and many behavioral signs of morphine withdrawal; and (2) may have therapeutic effects in man for the treatment of opiate withdrawal. PMID:10218862

  18. Safe intravenous thrombolysis in acute stroke despite treatment with rivaroxaban.

    PubMed

    Bornkamm, Katharina; Harloff, Andreas

    2014-11-01

    Data regarding intravenous thrombolysis in stroke patients receiving new oral anticoagulant drugs (nOAC) is sparse. In the near future, however, an increasing number of patients with atrial fibrillation will suffer recurrent stroke despite treatment with nOAC. This will cause a significant therapeutic dilemma as thrombolysis is contraindicated under such circumstances. We describe an 81-year-old patient presenting with acute ischemic stroke who was successfully treated with intravenous thrombolysis despite ongoing treatment with rivaroxaban. Our case report indicates that thrombolysis under nOAC may be safe under certain conditions and emphasizes the importance of establishing and performing specific anticoagulation tests for nOAC. PMID:24938385

  19. Filgrastim for the treatment of hematopoietic acute radiation syndrome.

    PubMed

    Farese, A M; MacVittie, T J

    2015-09-01

    The U.S. Food and Drug Administration (FDA) recently approved Neupogen(®) (filgrastim) for the treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident. It is the first medical countermeasure currently approved by the FDA for this indication under the criteria of the FDA "animal rule". This article summarizes the consequences of high-dose radiation exposure, a description of the hematopoietic acute radiation syndrome (H-ARS), the use of hematopoietic growth factors in radiation accident victims and current available treatments for H-ARS with an emphasis on the use of Neupogen in this scenario. PMID:26488033

  20. Treatment of Neuromyelitis Optica Spectrum Disorder: Acute, Preventive, and Symptomatic

    PubMed Central

    Kessler, Remi A.; Mealy, Maureen A.; Levy, Michael

    2016-01-01

    Opinion statement Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that primarily attacks the optic nerves and spinal cord leading to blindness and paralysis. The spectrum of the disease has expanded based on the specificity of the autoimmune response to the aquaporin-4 water channel on astrocytes. With wider recognition of NMOSD, a standard of care for treatment of this condition has condition based on a growing series of retrospective and prospective studies. This review covers the present state of the field in the treatment of acute relapses, preventive approaches, and therapies for symptoms of NMOSD. PMID:26705758

  1. Bifunctional Peptide-Based Opioid Agonist-Nociceptin Antagonist Ligands for Dual Treatment of Acute and Neuropathic Pain.

    PubMed

    Guillemyn, Karel; Starnowska, Joanna; Lagard, Camille; Dyniewicz, Jolanta; Rojewska, Ewelina; Mika, Joanna; Chung, Nga N; Utard, Valérie; Kosson, Piotr; Lipkowski, Andrzej W; Chevillard, Lucie; Arranz-Gibert, Pol; Teixidó, Meritxell; Megarbane, Bruno; Tourwé, Dirk; Simonin, Frédéric; Przewlocka, Barbara; Schiller, Peter W; Ballet, Steven

    2016-04-28

    Herein, the opioid pharmacophore H-Dmt-d-Arg-Aba-β-Ala-NH2 (7) was linked to peptide ligands for the nociceptin receptor. Combination of 7 and NOP ligands (e.g., H-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) led to binding affinities in the low nanomolar domain. In vitro, the hybrids behaved as agonists at the opioid receptors and antagonists at the nociceptin receptor. Intravenous administration of hybrid 13a (H-Dmt-d-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) to mice resulted in potent and long lasting antinociception in the tail-flick test, indicating that 13a was able to permeate the BBB. This was further supported by a cell-based BBB model. All hybrids alleviated allodynia and hyperalgesia in neuropathic pain models. Especially with respect to hyperalgesia, they showed to be more effective than the parent compounds. Hybrid 13a did not result in significant respiratory depression, in contrast to an equipotent analgesic dose of morphine. These hybrids hence represent a promising avenue toward analgesics for the dual treatment of acute and neuropathic pain. PMID:27035422

  2. Morphine differentially regulates hsp90beta expression in the nucleus accumbens of Lewis and Fischer 344 rats.

    PubMed

    Salas, Elisabet; Alonso, Elba; Sevillano, Julio; Herradon, Gonzalo; Bocos, Carlos; Morales, Lidia; Ramos, Maria Pilar; Alguacil, Luis Fernando

    2007-07-12

    We have comparatively studied hsp90beta gene and protein expression in the nucleus accumbens of Lewis and Fischer 344 (F344) rats, two inbred strains that exhibit prominent behavioural differences in drug-seeking behaviours. Phenotypical studies confirmed that Lewis rats developed a higher preference for morphine-paired environments after conditioning. RT-PCR assays did not reveal strain-related differences in hsp90beta gene expression in basal conditions; however, acute morphine treatment provoked an increase of hsp90beta mRNA 2h after injection only in the case of Lewis rats. We also found a significant upregulation of the Hsp90beta protein in both strains 8h after morphine injection, this increase being significantly higher in Lewis rats. Taking into account the suggested roles for Hsp90 in the brain, the data suggest that Lewis and F344 strain differences concerning opioid-seeking behaviours could be related to differential sensitivity to opioid-induced neuronal plasticity within the brain reward system, an effect that could be mediated (at least partially) by stress proteins. PMID:17562399

  3. Toll-Like Receptor 4 Mutant and Null Mice Retain Morphine-Induced Tolerance, Hyperalgesia, and Physical Dependence

    PubMed Central

    Mattioli, Theresa Alexandra; Leduc-Pessah, Heather; Skelhorne-Gross, Graham; Nicol, Christopher J. B.; Milne, Brian; Trang, Tuan; Cahill, Catherine M.

    2014-01-01

    The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4). Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal) were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (−) naloxone, an opioid receptor antagonist, and (+) naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence. PMID:24824631

  4. Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus.

    PubMed

    Miller, Laurence L; Altarifi, Ahmad A; Negus, S Stevens

    2015-10-01

    Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were 3 main findings. First, initial morphine exposure to drug naïve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for 6 days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. PMID:26375515

  5. Vasodilator treatment for acute and chronic heart failure.

    PubMed Central

    Chatterjee, K; Parmley, W W

    1977-01-01

    The current status of the use of vasodilator drugs in the treatment of acute and chronic heart failure has been reviewed. It is apparent that vasodilator treatment can be used effectively in some patients with heart failure with a beneficial haemodynamics response, and that vasodilator agents are likely to find an important place in the management of such patients. Vasodilator treatment may be associated with complications and must be used with care. Though several nonparenteral vasodilator agents have been investigated, no ideal drug is yet available for the treatment of chronic heart failure. Nevertheless, it is probable that suitable drugs will emerge and find an important place in the management of such patients. Images PMID:884021

  6. Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques.

    PubMed

    Weed, Michael R; Carruth, Lucy M; Adams, Robert J; Ator, Nancy A; Hienz, Robert D

    2006-09-01

    The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells. PMID:18040802

  7. Treatment of Orbital Complications Following Acute Rhinosinusitis in Children

    PubMed Central

    Wan, Yuzhu; Shi, Guanggang; Wang, Haibo

    2016-01-01

    Background: The orbital complications account for about 80% of all complications secondary to acute rhinosinusitis. If the treatment is not correct and in time, orbital complications could progress rapidly, leading to optic neuritis, cavernous sinus thrombophlebitis or life-threatening intracranial complications. Aims: To evaluate the therapeutic efficacy of conservative therapy for the patients with orbital cellulitis and endoscopic sinus surgery (ESS) performed on patients with subperiosteal abscess (SPA) secondary to acute rhinosinusitis in children. Study Design: Retrospective cross-sectional study. Methods: The retrospective study included 31 pediatric patients with orbital complications secondary to acute rhinosinusitis. In all cases, intensive treatment was initiated with a combination of oral or intravenous antibiotics, glucocorticoid and gelomyrtol forte after admission. ESS was performed if an improvement in the condition of patients did not occur after 48 hours. However, the patients with orbital SPA, motility disorders of eyeball or decreased vision received ESS immediately within 24 hours. Results: Sixteen patients were cured by conservative therapy and 15 patients by ESS. All of the signs and symptoms disappeared after conservative therapy or ESS. There were no recurrences within the follow-up period of 1 to 8 years. Conclusion: Conservative therapy is an effective method for patients with inflammatory edema and most cases of orbital cellulitis in children. SPA can be cured by ESS. PMID:27606135

  8. Treatment of acute limb ischemia with focus on endovascular techniques.

    PubMed

    Zeller, T; Tepe, G

    2009-05-01

    Acute limb ischemia is still the most frequent cause of major limb loss. Timely and fast revascularization is the key for limb salvage and patient survival. Large randomized trials showed equivalency of surgical and endovascular revascularization by means of local lysis with urokinase (TOPAS, STILE). New lytic agents and their modified application such as via a pulse spray catheter or combined with an ultrasound catheter and the combination with glycoprotein IIb/IIIa receptor antagonists have increased the efficacy and speed of thrombolysis. Recently, mechanical thrombectomy devices have become more widespread because intervention time and bleeding complications can be reduced. This review article summarizes the clinical presentation of and the treatment options for acute arterial occlusive disease caused either by embolism or local thrombosis. PMID:19588300

  9. [Treatment of acute myocardial infarction--an elucidative report].

    PubMed

    Madsen, E B; Godtfredsen, J; Hansen, J F; Jensen, G; Nielsen, B L; Nielsen, P E; Nielsen, T T; Pedersen, A; Rømer, F; Sandøe, E

    1989-06-01

    The present-day optimal treatment of patients with acute myocardial infarction (AMI) is reviewed. The prehospital phase should be as brief as possible. Emergency observation and treatment in hospital should be initiated without delay. Schematic stages for mobilization have been discarded and free mobilization is recommended. Routine acute intervention with thrombolysis is recommended for patients in whom symptoms have been present for 6-12 hours and treatment with Aspirin is recommended. Beta-blocking agents are recommended for patients with increased risk after discharge. Treatment of ventricular and supraventricular arrhythmias, block and cardiac failure are reviewed in detail. Patients without complications should be monitored for three to five days and may be discharged after seven to ten days. Exercise ECG should be carried out at discharge to assess the working capacity, ischaemia and subjective reaction. The importance of good patient information is emphasized. Cessation of smoking, control of lipids and blood pressure are important as secondary interventions. As far as possible, outpatient control should be offered after discharge. The criteria for referral to specialized cardiological departments are established both for emergency and elective referral. Patients under the age of 70 years with high risk for repeated AMI or death after discharge (with residual ischaemia) should possibly be referred for coronary arteriography. PMID:2567543

  10. Attenuation of tolerance to opioid-induced antinociception and protection against morphine-induced decrease of neurofilament proteins by idazoxan and other I2-imidazoline ligands

    PubMed Central

    Boronat, M Assumpció; Olmos, Gabriel; García-Sevilla, Jesús A

    1998-01-01

    Agmatine, the proposed endogenous ligand for imidazoline receptors, has been shown to attenuate tolerance to morphine-induced antinociception (Kolesnikov et al., 1996). The main aim of this study was to assess if idazoxan, an α2-adrenoceptor antagonist that also interacts with imidazoline receptors, could also modulate opioid tolerance in rats and to establish which type of imidazoline receptors (or other receptors) are involved. Antinociceptive responses to opioid drugs were determined by the tail-flick test. The acute administration of morphine (10 mg kg−1, i.p., 30 min) or pentazocine (10 mg kg−1, i.p., 30 min) resulted in marked increases in tail-flick latencies (TFLs). As expected, the initial antinociceptive response to the opiates was lost after chronic (13 days) treatment (tolerance). When idazoxan (10 mg kg−1, i.p.) was given chronically 30 min before the opiates it completely prevented morphine tolerance and markedly attenuated tolerance to pentazocine (TFLs increased by 71–143% at day 13). Idazoxan alone did not modify TFLs. The concurrent chronic administration (10 mg kg−1, i.p., 13 days) of 2-BFI, LSL 60101, and LSL 61122 (valldemossine), selective and potent I2-imidazoline receptor ligands, and morphine (10 mg kg−1, i.p.), also prevented or attenuated morphine tolerance (TFLs increased by 64–172% at day 13). This attenuation of morphine tolerance was still apparent six days after discontinuation of the chronic treatment with LSL 60101-morphine. The acute treatment with these drugs did not potentiate morphine-induced antinociception. These drugs alone did not modify TFLs. Together, these results indicated the specific involvement of I2-imidazoline receptors in the modulation of opioid tolerance. The concurrent chronic (13 days) administration of RX821002 (10 mg kg−1, i.p.) and RS-15385-197 (1 mg kg−1, i.p.), selective α2-adrenoceptor antagonists, and morphine (10 mg kg−1, i.p.), did not

  11. Magnetic resonance imaging in acute ischemic stroke treatment.

    PubMed

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven; Kang, Dong-Wha

    2014-09-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872

  12. Magnetic Resonance Imaging in Acute Ischemic Stroke Treatment

    PubMed Central

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven

    2014-01-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872

  13. Economic evaluation of treatment for acute lymphoblastic leukaemia in childhood.

    PubMed

    Rae, C; Furlong, W; Jankovic, M; Moghrabi, Albert; Naqvi, A; Sala, A; Samson, Y; DePauw, S; Feeny, D; Barr, R

    2014-11-01

    Berlin-Frankfurt-Munster (BFM) and Dana-Farber Cancer Institute (DFCI) consortia's treatment strategies for acute lymphoblastic leukaemia (ALL) in children are widely used. We compared the health effects and monetary costs of hospital treatments for these two strategies. Parents of children treated at seven centres in Canada, Italy and the USA completed health-related quality of life (HRQL) assessments during four active treatment phases and at 2 years after treatment. Mean HRQL scores were used to calculate quality-adjusted life years (QALYs) for a period of 5 years following diagnosis. Total costs of treatment were determined from variables in administrative databases in a universally accessible and publicly funded healthcare system. Valid HRQL assessments (n = 1200) were collected for 307 BFM and 317 DFCI patients, with costs measured for 66 BFM and 28 DFCI patients. QALYs per patient were <1.0% greater for BFM than DFCI. Median HRQL scores revealed no difference in QALYs. The difference in mean total costs for BFM (US$88 480) and DFCI (US$93 026) was not significant (P = 0.600). This study provides no evidence of superiority for one treatment strategy over the other. Current BFM or DFCI strategies should represent conventional management for the next economic evaluation of treatments for ALL in childhood. PMID:24393150

  14. Acute treatment of migraine and the role of triptans.

    PubMed

    Freitag, F G

    2001-03-01

    The use of triptans has improved the ability to treat migraine successfully compared with older treatments. Speed of relief, consistency of effect, and good tolerability have been the hallmarks of these agents. All of the currently available triptans have comparable efficacy and tolerability. Variables between the agents may lead to one agent or dose form being preferred over another in various clinical scenarios. The triptans that are forthcoming may improve on these options through enhanced efficacy rates, tolerability, and headache recurrence rates. There exist increasing options for migraine treatment that may further improve the clinical effects of the older and newer triptans through early treatment of migraine at the stages of mild migraine pain, or even during the prodromal phase of the attack. Additionally, recent work suggests that mini-prophylaxis of migraine at the menses is a highly successful treatment option with the triptans. In this age of managed care, providing cost-effective treatment of headache will take on increasing importance. Techniques such as stratification of acute treatments may enhance cost-effective care, whereas ready availability of the triptans may lead to significant improvements in utilization of parameters such as office visits, emergency room treatment, and even hospitalization. PMID:11898508

  15. Prospects for the temporary treatment of acute liver failure.

    PubMed

    Stockmann, Hein B A C; IJzermans, Jan N M

    2002-02-01

    At present, the most successful treatment of acute liver failure is orthotopic liver transplantation, with survival rates ranging from 70% to 85%. However, mortality rates for liver failure remain high because of the shortage of available donor organs. Therefore, there has been renewed interest in temporary treatment methods for patients with acute liver failure to either allow liver regeneration or await liver transplantation. It is thought that the function of the liver can only be replaced with the biological substrate, e.g. liver cells or a whole liver specimen, which requires the availability of liver tissue from xenogeneic or human sources. In this review, existing temporary liver support techniques are summarized and the potential hazards are described. These include the immunological implications of these techniques, e.g. the host versus graft reaction, which may influence the effectivity of the support system, and in the long run may sensitize the patient to subsequent allogeneic transplantation. The graft versus host reaction is also considered. At present, one of the major concerns is the threat of pig-to-human transmission of activated endogenous retrovirus present in the pig genome. An overview is given of literature concerning the transmission of retrovirus particles in vitro and in vivo. Finally, new solutions for the development of ex vivo systems for temporary treatment of patients with acute liver failure are discussed. These include the use of new immortalized human cell lines and human fetal hepatocytes, and the possibility of isolating, expanding and genetically manipulating stem cells in order to have stable differentiated and committed cells. PMID:11981346

  16. WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis.

    PubMed

    Di Saverio, Salomone; Birindelli, Arianna; Kelly, Micheal D; Catena, Fausto; Weber, Dieter G; Sartelli, Massimo; Sugrue, Michael; De Moya, Mark; Gomes, Carlos Augusto; Bhangu, Aneel; Agresta, Ferdinando; Moore, Ernest E; Soreide, Kjetil; Griffiths, Ewen; De Castro, Steve; Kashuk, Jeffry; Kluger, Yoram; Leppaniemi, Ari; Ansaloni, Luca; Andersson, Manne; Coccolini, Federico; Coimbra, Raul; Gurusamy, Kurinchi S; Campanile, Fabio Cesare; Biffl, Walter; Chiara, Osvaldo; Moore, Fred; Peitzman, Andrew B; Fraga, Gustavo P; Costa, David; Maier, Ronald V; Rizoli, Sandro; Balogh, Zsolt J; Bendinelli, Cino; Cirocchi, Roberto; Tonini, Valeria; Piccinini, Alice; Tugnoli, Gregorio; Jovine, Elio; Persiani, Roberto; Biondi, Antonio; Scalea, Thomas; Stahel, Philip; Ivatury, Rao; Velmahos, George; Andersson, Roland

    2016-01-01

    Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics. PMID:27437029

  17. Treatment of acute thoracic aortic syndromes using endovascular techniques

    PubMed Central

    Uğuz, Emrah; Canyiğit, Murat; Hıdıroğlu, Mete; Şener, Erol

    2016-01-01

    PURPOSE Acute thoracic aortic syndrome (ATAS) is a novel term to define emergency aortic conditions with common clinical features and challenges. Traditional management of ATAS includes surgical replacement of the aorta and is correlated with high perioperative mortality and morbidity. We aimed to evaluate our experience and outcomes in patients presenting with ATAS, managed by endovascular techniques. METHODS This cohort consisted of 31 consecutive patients (24 males; mean age, 57.5±13.81 years; range, 19–84 years) with acute thoracic aortic pathologies who underwent endovascular repair between January 2011 and January 2015. The study was designed as a retrospective analysis of prospectively maintained data. RESULTS Complicated acute type-B aortic dissection was the most common pathology (35.5%). All aortic stent-grafts (n=37) and dissection stents (n=9) were implanted with 100% procedural success. The overall in-hospital mortality was 9.7%. The mean follow-up duration of patients who were alive at 30 days was 25.9±11.49 months (3–53 months). So far, there have been no late deaths after 30 days. CONCLUSION In the high-risk setting of ATAS, endovascular procedures come forward as novel therapeutic strategies with promising results. Endovascular repair of ATAS can be considered as a first-line treatment alternative under emergency conditions with encouraging results, particularly when conventional surgical repair cannot be implemented due to prohibitive comorbidities. PMID:27113420

  18. Protective role of taurine against morphine-induced neurotoxicity in C6 cells via inhibition of oxidative stress.

    PubMed

    Zhou, Jiaqing; Li, Yan; Yan, Guangyan; Bu, Qian; Lv, Lei; Yang, Yanzhu; Zhao, Jinxuan; Shao, Xue; Deng, Yi; Zhu, Ruimin; Zhao, Yinglan; Cen, Xiaobo

    2011-11-01

    This study was carried out to investigate the protective role of taurine (2-aminoethanesulphonicacid) against morphine-induced neurotoxicity in C6 cells. It was found that taurine significantly increased the viability of C6 cells treated by morphine, showing the neuroprotective role against morphine-induced neurotoxicity. However, such neuroprotective effect of taurine could not be blocked by bicuculline, an antagonist of gamma-amino butyrate (GABA) receptor. To determine the oxidative damage induced by morphine, the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured in C6 cells. The decreased activities of SOD, CAT, and GPx in C6 cells were observed after morphine treatment for 48 h. However, taurine administration effectively ameliorated morphine-induced oxidative insult. To estimate anti-apoptosis effect of taurine, flow cytometry analysis as well as detection for caspase-3 and Bcl-2 expressions was performed after morphine exposure for 48 h. It was found that Bcl-2 expression was down regulated by morphine, whereas taurine could reverse morphine-induced decrease in Bcl-2 expression. Taurine showed no effect on caspase-3 expression. Collectively, the results show that taurine possesses the capability to ameliorate morphine-induced oxidative insult and apoptosis in C6 cells, probably due to its antioxidant activity rather than activation of GABA receptors. PMID:21611853

  19. Distinct expression of synaptic NR2A and NR2B in the central nervous system and impaired morphine tolerance and physical dependence in mice deficient in postsynaptic density-93 protein

    PubMed Central

    Liaw, Wen-Jinn; Zhu, Xu-Guang; Yaster, Myron; Johns, Roger A; Gauda, Estelle B; Tao, Yuan-Xiang

    2008-01-01

    Postsynaptic density (PSD)-93, a neuronal scaffolding protein, binds to and clusters N-methyl-D-aspartate receptor (NMDAR) subunits NR2A and NR2B at cellular membranes in vitro. However, the roles of PSD-93 in synaptic NR2A and NR2B targeting in the central nervous system and NMDAR-dependent physiologic and pathologic processes are still unclear. We report here that PSD-93 deficiency significantly decreased the amount of NR2A and NR2B in the synaptosomal membrane fractions derived from spinal cord dorsal horn and forebrain cortex but did not change their levels in the total soluble fraction from either region. However, PSD-93 deficiency did not markedly change the amounts of NR2A and NR2B in either synaptosomal or total soluble fractions from cerebellum. In mice deficient in PSD-93, morphine dose-dependent curve failed to shift significantly rightward as it did in wild type (WT) mice after acute and chronic morphine challenge. Unlike WT mice, PSD-93 knockout mice also showed marked losses of NMDAR-dependent morphine analgesic tolerance and associated abnormal sensitivity in response to mechanical, noxious thermal, and formalin-induced inflammatory stimuli after repeated morphine injection. In addition, PSD-93 knockout mice displayed dramatic loss of jumping activity, a typical NMDAR-mediated morphine withdrawal abstinence behavior. These findings indicate that impaired NMDAR-dependent neuronal plasticity following repeated morphine injection in PSD-93 knockout mice is attributed to PSD-93 deletion-induced alterations of synaptic NR2A and NR2B expression in dorsal horn and forebrain cortex neurons. The selective effect of PSD-93 deletion on synaptic NMDAR expression in these two major pain-related regions might provide the better strategies for the prevention and treatment of opioid tolerance and physical dependence. PMID:18851757

  20. Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge.

    PubMed

    May, Walter J; Henderson, Fraser; Gruber, Ryan B; Discala, Joseph F; Young, Alex P; Bates, James N; Palmer, Lisa A; Lewis, Stephen J

    2013-08-28

    This study explored the concept that morphine has latent deleterious actions on the ventilatory control systems that respond to a hypoxic-hypercapnic challenge. In this study, we examined the ventilatory responses elicited by hypoxic-hypercapnic challenge in conscious rats at a time when the effects of morphine (10 mg/kg) on arterial blood-gas chemistry and minute ventilation had subsided. Morphine induced pronounced changes in arterial blood-gas chemistry (e.g., an increase in pCO2, decreases in pO2 and sO2) and decreases in minute ventilation. Despite the complete resolution of the morphine-induced changes in arterial blood-gas chemistry and minute ventilation and almost complete resolution of the effects on peak inspiratory flow and peak expiratory flow, subsequent exposure to hypoxic-hypercapnic challenge elicited markedly blunted increases in minute ventilation and in peak inspiratory and expiratory flows. These findings demonstrate that (1) the changes in arterial blood-gas chemistry elicited by morphine parallel changes in minute ventilation rather than PIF and PEF, and (2) morphine has latent untoward effects on the ventilatory responses to hypoxic-hypercapnic challenge. These novel findings raise the possibility that patients deemed to have recovered from the acute ventilatory depressant effects of morphine may still be susceptible to the latent effects of this opioid analgesic. The mechanisms underlying these latent effects remain to be elucidated. PMID:25045592

  1. Reversal of morphine analgesic tolerance by ethanol in the mouse.

    PubMed

    Hull, L C; Gabra, B H; Bailey, C P; Henderson, G; Dewey, W L

    2013-06-01

    The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However, chronic opioid use is often made more dangerous by the coconsumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals who died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross-tolerance between [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the γ-aminobutyric acid (GABA)(B) receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABA(A) antagonist bicuculline but not by the GABA(B) antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment. PMID:23528610

  2. Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse

    PubMed Central

    Hull, L. C.; Gabra, B. H.; Bailey, C. P.; Henderson, G.

    2013-01-01

    The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However, chronic opioid use is often made more dangerous by the coconsumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals who died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross-tolerance between [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the γ-aminobutyric acid (GABA)B receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABAA antagonist bicuculline but not by the GABAB antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment. PMID:23528610

  3. A systematic review on the treatment of acute ankle sprain: brace versus other functional treatment types.

    PubMed

    Kemler, Ellen; van de Port, Ingrid; Backx, Frank; van Dijk, C Niek

    2011-03-01

    Ankle injuries, especially ankle sprains, are a common problem in sports and medical care. Ankle sprains result in pain and absenteeism from work and/or sports participation, and can lead to physical restrictions such as ankle instability. Nowadays, treatment of ankle injury basically consists of taping the ankle. The purpose of this review is to evaluate the effectiveness of ankle braces as a treatment for acute ankle sprains compared with other types of functional treatments such as ankle tape and elastic bandages. A computerized literature search was conducted using PubMed, EMBASE, CINAHL and the Cochrane Clinical Trial Register. This review includes randomized controlled trials in English, German and Dutch, published between 1990 and April 2009 that compared ankle braces as a treatment for lateral ankle sprains with other functional treatments. The inclusion criteria for this systematic review were (i) individuals (sports participants as well as non-sports participants) with an acute injury of the ankle (acute ankle sprains); (ii) use of an ankle brace as primary treatment for acute ankle sprains; (iii) control interventions including any other type of functional treatment (e.g. Tubigrip™, elastic wrap or ankle tape); and (iv) one of the following reported outcome measures: re-injuries, symptoms (pain, swelling, instability), functional outcomes and/or time to resumption of sports, daily activities and/or work. Eight studies met all inclusion criteria. Differences in outcome measures, intervention types and patient characteristics precluded pooling of the results, so best evidence syntheses were conducted. A few individual studies reported positive outcomes after treatment with an ankle brace compared with other functional methods, but our best evidence syntheses only demonstrated a better treatment result in terms of functional outcome. Other studies have suggested that ankle brace treatment is a more cost-effective method, so the use of braces after acute

  4. BK channels in microglia are required for morphine-induced hyperalgesia.

    PubMed

    Hayashi, Yoshinori; Morinaga, Saori; Zhang, Jing; Satoh, Yasushi; Meredith, Andrea L; Nakata, Takahiro; Wu, Zhou; Kohsaka, Shinichi; Inoue, Kazuhide; Nakanishi, Hiroshi

    2016-01-01

    Although morphine is a gold standard medication, long-term opioid use is associated with serious side effects, such as morphine-induced hyperalgesia (MIH) and anti-nociceptive tolerance. Microglia-to-neuron signalling is critically involved in pain hypersensitivity. However, molecules that control microglial cellular state under chronic morphine treatment remain unknown. Here we show that the microglia-specific subtype of Ca(2+)-activated K(+) (BK) channel is responsible for generation of MIH and anti-nociceptive tolerance. We find that, after chronic morphine administration, an increase in arachidonic acid levels through the μ-opioid receptors leads to the sole activation of microglial BK channels in the spinal cord. Silencing BK channel auxiliary β3 subunit significantly attenuates the generation of MIH and anti-nociceptive tolerance, and increases neurotransmission after chronic morphine administration. Therefore, microglia-specific BK channels contribute to the generation of MIH and anti-nociceptive tolerance. PMID:27241733

  5. BK channels in microglia are required for morphine-induced hyperalgesia

    PubMed Central

    Hayashi, Yoshinori; Morinaga, Saori; Zhang, Jing; Satoh, Yasushi; Meredith, Andrea L.; Nakata, Takahiro; Wu, Zhou; Kohsaka, Shinichi; Inoue, Kazuhide; Nakanishi, Hiroshi

    2016-01-01

    Although morphine is a gold standard medication, long-term opioid use is associated with serious side effects, such as morphine-induced hyperalgesia (MIH) and anti-nociceptive tolerance. Microglia-to-neuron signalling is critically involved in pain hypersensitivity. However, molecules that control microglial cellular state under chronic morphine treatment remain unknown. Here we show that the microglia-specific subtype of Ca2+-activated K+ (BK) channel is responsible for generation of MIH and anti-nociceptive tolerance. We find that, after chronic morphine administration, an increase in arachidonic acid levels through the μ-opioid receptors leads to the sole activation of microglial BK channels in the spinal cord. Silencing BK channel auxiliary β3 subunit significantly attenuates the generation of MIH and anti-nociceptive tolerance, and increases neurotransmission after chronic morphine administration. Therefore, microglia-specific BK channels contribute to the generation of MIH and anti-nociceptive tolerance. PMID:27241733

  6. Diagnosis and treatment of acute low back pain.

    PubMed

    Casazza, Brian A

    2012-02-15

    Acute low back pain is one of the most common reasons for adults to see a family physician. Although most patients recover quickly with minimal treatment, proper evaluation is imperative to identify rare cases of serious underlying pathology. Certain red flags should prompt aggressive treatment or referral to a spine specialist, whereas others are less concerning. Serious red flags include significant trauma related to age (i.e., injury related to a fall from a height or motor vehicle crash in a young patient, or from a minor fall or heavy lifting in a patient with osteoporosis or possible osteoporosis), major or progressive motor or sensory deficit, new-onset bowel or bladder incontinence or urinary retention, loss of anal sphincter tone, saddle anesthesia, history of cancer metastatic to bone, and suspected spinal infection. Without clinical signs of serious pathology, diagnostic imaging and laboratory testing often are not required. Although there are numerous treatments for nonspecific acute low back pain, most have little evidence of benefit. Patient education and medications such as nonsteroidal anti-inflammatory drugs, acetaminophen, and muscle relaxants are beneficial. Bed rest should be avoided if possible. Exercises directed by a physical therapist, such as the McKenzie method and spine stabilization exercises, may decrease recurrent pain and need for health care services. Spinal manipulation and chiropractic techniques are no more effective than established medical treatments, and adding them to established treatments does not improve outcomes. No substantial benefit has been shown with oral steroids, acupuncture, massage, traction, lumbar supports, or regular exercise programs. PMID:22335313

  7. The role of orexin type-1 receptors in the development of morphine tolerance in locus coeruleus neurons: An electrophysiological perspective.

    PubMed

    Abdollahi, Hakime; Ghaemi-Jandabi, Masoumeh; Azizi, Hossein; Semnanian, Saeed

    2016-09-01

    Long-term exposure to opioid agonists results in tolerance to their analgesic effects, so the effectiveness of opioid agonists in the management of pain becomes limited. The locus coeruleus (LC) nucleus has been involved in the development of tolerance to opiates. Orexin type-1 receptors (OX1Rs) are highly expressed in LC nucleus. Orexin plays a noteworthy role in the occurrence of morphine tolerance. The purpose of the present study is to investigate the role of orexin type-1 receptors in the development of morphine tolerance in LC neurons. In this study, adult male Wistar rats weighing 250-300g were utilized. Induction of morphine tolerance was obtained by single injection of morphine per day for 6 successive days. An orexin type-1 receptor antagonist (SB-334867) was injected into the lateral ventricle instantly prior to morphine injection. On day 7, the effect of morphine on the electrical activity of LC neurons was studied using in vivo extracellular single unit recording. The results demonstrate that morphine injection for 6 consecutive days led to the development of morphine-induced tolerance in LC neurons. In other words, there was a significant decrease in LC neuronal responsiveness to morphine injection. Inhibitory responses of LC neurons to intraperitoneally applied morphine can be observed with the treatment of the SB-334867 prior to morphine injection. This study showed that OX1R blockade by SB-334867 prevents the development of morphine tolerance in LC neurons. We hope that further studies will lead to considerable progress in understanding the molecular adaptations that contribute to morphine tolerance. PMID:27235867

  8. Naloxone affects both pharmacokinetics and pharmacodynamics of morphine. Application of direct correlation analysis.

    PubMed

    Shibanoki, S; Kubo, T; Kogure, M; Ishikawa, K

    1991-08-01

    Direct correlation analyses between the distribution of morphine (pharmacokinetics) and the biochemical effects of the drug on monoamine metabolism (pharmacodynamics) are reported for dissected regions of the brain. Determinations of morphine and monoamine-related substances were carried out in the same sample by high performance liquid chromatography with electrochemical detection. Naloxone, an antagonist of morphine, significantly shortened the biological half lives of morphine in both the blood and brain tissue. Such pharmacokinetic behavior appeared to be related to the contractive effect of morphine on the bile duct, and naloxone facilitated the excretion of morphine via this route. In the striatum, significant correlations were observed between the concentrations of the metabolites of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and morphine with a shift to the right in the concentration-response curve on naloxone treatment indicating competitive antagonism. While significant correlations were also observed in this brain region for the metabolites of noradrenaline, 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), and 5-hydroxytryptamine, 5-hydroxyindoleacetic acid (5-HIAA), a shift to the right did not occur. Significant correlations and shifts were noted for DOPAC, HVA and MOPEG in the hypothalamus. However, no correlation was found between the concentrations of 5-HIAA and morphine in this region. In other regions such as the hippocampus and medulla oblongata, similar correlations and shifts were not observed for MOPEG and 5-HIAA or for DOPAC and HVA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1714733

  9. A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats

    PubMed Central

    Li, Qian-Qian; Sun, Cheng-Yu; Luo, Yi-Xiao; Xue, Yan-Xue; Meng, Shi-Qiu; Xu, Ling-Zhi; Chen, Na; Deng, Jia-Hui; Zhai, Hai-Feng; Kosten, Thomas R.; Shi, Jie

    2015-01-01

    Background: Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies. Methods: A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized with 6-glutarylmorphine as the hapten and a lengthened linker of 6 carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed. Results: After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse. Conclusion: These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin. PMID:25522425

  10. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl− homeostasis

    PubMed Central

    Ferrini, Francesco; Trang, Tuan; Mattioli, Theresa-Alexandra M.; Laffray, Sophie; Del’Guidice, Thomas; Lorenzo, Louis-Etienne; Castonguay, Annie; Doyon, Nicolas; Zhang, Wenbo; Godin, Antoine G.; Mohr, Daniela; Beggs, Simon; Vandal, Karen; Beaulieu, Jean-Martin; Cahill, Catherine; Salter, Michael W.; De Koninck, Yves

    2016-01-01

    A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opiates. We show here that hyperalgesia-inducing treatment with morphine causes downregulation of the K+-Cl− cotransporter KCC2, impairing Cl− homeostasis in spinal lamina l neurons. Restoring Eanion reversed the morphine-induced hyperalgesia without affecting tolerance. The hyperalgesia was also reversed by ablating spinal microglia. Morphine hyperalgesia, but not tolerance, required μ opioid receptor-dependent expression of P2X4 receptors (P2X4Rs) in microglia and μ-independent gating of the release of brain-derived neurotrophic factor (BDNF) by P2X4Rs. Blocking BDNF-TrkB signalling preserved Cl− homeostasis and reversed the hyperalgesia. Gene-targeted mice in which BDNF was deleted from microglia did not develop hyperalgesia to morphine. Yet, neither morphine antinociception nor tolerance was affected in these animals. Our findings dissociate morphine-induced hyperalgesia from tolerance and unveil the microglia-to-neuron P2X4-BDNF-KCC2 pathway as a therapeutic target to prevent hyperalgesia without affecting morphine analgesia. PMID:23292683

  11. Rural treatment of acute cardiogenic pulmonary edema: applying the evidence to achieve success with failure.

    PubMed

    Bosomworth, John

    2008-01-01

    Rural management of acute cardiogenic pulmonary edema should be based on avoidance of adverse outcomes such as in-hospital mortality, the need for intensive care unit care, and the need for intubation and mechanical ventilation. Current evidence suggests that early noninvasive continuous positive airway pressure and early aggressive preload reduction with intravenous nitroglycerin are first-line interventions. Afterload reduction with sublingual captopril, with or without nitroglycerin, improves outcomes and is a second-line intervention. Furosemide is associated with adverse outcomes when used alone and should be given only after vasodilator therapy as a third-line intervention. Inotropes should be used only with demonstrably poor perfusion as they do not improve outcomes and may indeed be associated with increased mortality. Concurrent vasodilator therapy should be considered as soon as possible. Morphine should not be used as it is associated with adverse outcomes. If sedation is desirable, benzodiazepines should be considered. PMID:18796257

  12. Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys.

    PubMed

    Maguire, David R; Gerak, Lisa R; France, Charles P

    2016-04-01

    Opioid abusers discount delayed reinforcers more rapidly than nonusers; however, it is unclear whether chronic drug administration or its discontinuation impacts discounting. This study examined the impact of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Responding on one lever delivered one food pellet immediately; responding on another lever delivered two food pellets either immediately or after a delay (30-120 s) that increased within the session. Monkeys (n=3) responded for the large reinforcer when both reinforcers were delivered immediately and more for the smaller, immediately available reinforcer as the delay to delivery of the large reinforcer increased. When administered acutely, morphine (0.032-5.6 mg/kg) increased trial omissions and had variable effects on choice, with small doses decreasing and large doses increasing choice of the large delayed reinforcer. Chronic morphine administration (0.1 mg/kg/day to 3.2 mg/kg twice daily) reduced choice of the large delayed reinforcer in two monkeys, while increasing choice in a third monkey. Despite the development of tolerance to some effects (i.e. rightward shifts in dose-effect curves for the number of trials omitted) and evidence of mild opioid dependence (e.g. decrease in the number of trials completed, as well as body weight), discontinuation of treatment did not appear to systematically impact discounting. Overall, these results suggest that repeated opioid administration causes persistent effects on choice under a delay discounting procedure; however, differences in the direction of effect among individuals suggest that factors other than, or in addition to, changes in discounting might play a role. PMID:26397762

  13. Inhibition by morphine and morphine-like drugs of nicotine-induced emesis in cats.

    PubMed

    Beleslin, D B; Krstić, S K; Stefanović-Denić, K; Strbac, M; Mićić, D

    1981-05-01

    The effect of morphine, methadone and pethidine injected into the cerebral ventricle of the unanesthetized cat upon emesis produced by nicotine induced similarly was investigated. Morphine and morphine-like drugs depress or abolish the emetic effect of nicotine. The inhibitory effect of morphine, methadone and pethidine is observed after a transient emetic action of these drugs. The emetic and anti-emetic action of morphine, methadone and pethidine can perhaps be ascribed to an agonist/antagonist activity. Further, the possible site of inhibitory action of morphine and morphine-like drugs on the emesis produced by nicotine may be the area postrema of fourth ventricle. PMID:7248811

  14. Chronic Morphine Reduces Surface Expression of δ-Opioid Receptors in Subregions of Rostral Striatum.

    PubMed

    Leah, Paul M; Heath, Emily M L; Balleine, Bernard W; Christie, Macdonald J

    2016-03-01

    The delta opioid receptor (DOPr), whilst not the primary target of clinically used opioids, is involved in development of opioid tolerance and addiction. There is growing evidence that DOPr trafficking is involved in drug addiction, e.g., a range of studies have shown increased plasma membrane DOPr insertion during chronic treatment with opioids. The present study used a transgenic mouse model in which the C-terminal of the DOPr is tagged with enhanced-green fluorescence protein to examine the effects of chronic morphine treatment on surface membrane expression in striatal cholinergic interneurons that are implicated in motivated learning following both chronic morphine and morphine sensitization treatment schedules in male mice. A sex difference was noted throughout the anterior striatum, which was most prominent in the nucleus accumbens core region. Incontrast with previous studies in other neurons, chronic exposure to a high dose of morphine for 6 days had no effect, or slightly decreased (anterior dorsolateral striatum) surface DOPr expression. A morphine sensitization schedule produced similar results with a significant decrease in surface DOPr expression in nucleus accumbens shell. These results suggest that chronic morphine and morphine sensitisation treatment may have effects on instrumental reward-seeking behaviours and learning processes related to drug addiction, via effects on striatal DOPr function. PMID:26093651

  15. Site and mechanism of morphine tolerance in the gastrointestinal tract

    PubMed Central

    AKBARALI, H. I.; INKISAR, A.; DEWEY, W. L.

    2015-01-01

    Opioid-induced constipation is a major clinical problem. The effects of morphine, and other narcotics, on the gastrointestinal tract persist over long-term use thus limiting the clinical benefit of these excellent pain relievers. The effects of opioids in the gut, including morphine, are largely mediated by the μ-opioid receptors at the soma and nerve terminals of enteric neurons. Recent studies demonstrate that regional differences exist in both acute and chronic morphine along the gastrointestinal tract. While tolerance develops to the analgesic effects and upper gastrointestinal motility upon repeated morphine administration, tolerance does not develop in the colon with chronic opioids resulting in persistent constipation. Here, we review the mechanisms by which tolerance develops in the small but not the large intestine. The regional differences lie in the signaling and regulation of the μopioid receptor in the various segments of the gastrointestinal tract. The differential role of β-arrestin2 in tolerance development between central and enteric neurons defines the potential for therapeutic approaches in developing ligands with analgesic properties and minimal constipating effects. PMID:25257923

  16. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes

    PubMed Central

    Graham, Garth

    2016-01-01

    In the USA and internationally, women experience farranging differences with respect to acute coronary syndrome (ACS) and myocardial infarction (MI). Women suffer from more comorbidities than men, such as smoking, obesity, hypertension, diabetes, and poor mental health. They some-times exhibit atypical MI presentation symptoms and are overall less likely to present with chest pain. Women are more likely than men to encounter delays between the onset of symptoms and arrival at the hospital or to guideline treatment. The use of various surgical and pharmacological treatments, including revascularization approaches, also differs. Women, on average, have worse outcomes than men following MI, with more complications, higher mortality rates, and poorer recovery. Internationally, outcomes are similar despite various differences in health care and culture in non-US countries. In this review, we detail differences regarding ACS and MI in women, describing their complex correlations and discussing their possible causes. Educational approaches that are tailored to women might help to reduce the incidence of ACS and MI, as well as outcomes following hospitalization. Although outcomes following acute MI have been improving over the years, women may require special consideration in order to see continued improvement. PMID:26884685

  17. Pharmacological treatment of acute migraine in adolescents and children.

    PubMed

    Wöber-Bingöl, Çiçek

    2013-06-01

    Migraine is a common disease in children and adolescents. The incidence of migraine has increased alarmingly in the general population during recent decades. Migraine causes considerable individual suffering and impaired quality of life. Therefore, appropriate management is essential. In this article, the treatment of acute migraine in children and adolescents will be reviewed. Only a few randomized controlled studies have been published and high placebo rates are a major problem for proving superiority of active drugs. Generally, acetaminophen (paracetamol) and ibuprofen are accepted as drugs of first choice, even though the evidence is poor for the former and limited for latter. Among 14 studies on triptans in adolescents, 9 showed some superiority over placebo with respect to pain relief and pain freedom, and among 6 studies in children, 5 suggest some superiority over placebo. Sumatriptan nasal spray and zolmitriptan nasal spray have been approved for adolescents in Europe; almotriptan has been approved for adolescents in the USA, as has rizatriptan for patients aged 6-17 years. A recent study demonstrated the efficacy of a fixed combination of sumatriptan and naproxen in adolescents with migraine. In conclusion, evidence for the pharmacological treatment of acute migraine in children is very poor and evidence for adolescents is better but still limited. PMID:23575981

  18. An update of current treatments for adult acute myeloid leukemia

    PubMed Central

    Gardin, Claude

    2016-01-01

    Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose intensification and safer allogeneic HSCT procedures, allowing a larger proportion of patients to achieve durable remission. In addition, improved identification of patients at relatively low risk of relapse should limit their undue exposure to the risks of HSCT in first remission. The role of new effective agents, such as purine analogs or gemtuzumab ozogamicin, is still under investigation, whereas promising new targeted agents are under clinical development. In contrast, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. The availability of hypomethylating agents likely represents an encouraging first step for this latter population, and it is hoped will allow for more efficient combinations with novel agents. PMID:26660429

  19. Antibody-based treatment of acute myeloid leukaemia.

    PubMed

    Mulford, Deborah A; Jurcic, Joseph G

    2004-01-01

    Monoclonal antibodies have become an important treatment modality in cancer therapy. Genetically engineered chimaeric and humanised antibodies have demonstrated activity against a variety of tumours. Whereas the humanised anti-CD33 monoclonal antibody HuM195 has only modest activity against overt acute myeloid leukaemia (AML), it can eliminate minimal residual disease detectable by reverse transcription-polymerase chain reaction in acute promyelocytic leukaemia. High-dose radioimmunotherapy with beta-particle-emitting isotopes targeting CD33, CD45 and CD66 can potentially allow intensification of antileukaemic therapy before bone marrow transplantation. Conversely, alpha-particle immunotherapy with isotopes such as bismuth-213 or actinium-225 offers the possibility of selective tumour cell kill while sparing surrounding normal cells. Targeted chemotherapy with the anti-CD33-calicheamicin construct gemtuzumab ozogamicin has produced remissions as a single agent in patients with relapsed AML and appears promising when used in combination with standard chemotherapy in the treatment of newly diagnosed AML. PMID:14680472

  20. Clonazepam oral droplets for the treatment of acute epileptic seizures.

    PubMed

    Sakata, Osamu; Onishi, Hiraku; Machida, Yoshiharu

    2008-12-01

    Oral droplet formulations of clonazepam (CZ) were developed to examine their potentials as an alternative to i.v. administration for the treatment of acute epileptic seizures. Propylene glycol containing 2.5% (wt/wt) CZ with or without 5.0% (wt/wt) oleic acid (OA) was prepared as a solution by heating at 90 degrees C and subsequently lowering the temperature to 30 degrees C. The droplet (20 microL) was administered to the oral cavity between the lower gum and bottom lip before CZ precipitation started. With a droplet of propylene glycol loaded with 2.5% (wt/wt) CZ and 5.0% (wt/wt) OA, the plasma concentration reached 20 ng/mL (minimal effective concentration) within 10 min and was maintained between 20 and 60 ng/mL, less than a toxic level, for a period of 60 min. For a droplet of propylene glycol loaded only with CZ at 2.5% (wt/wt), it took more than 15 min for the plasma concentration to reach 20 ng/mL. It is suggested that a droplet of CZ/OA/propylene glycol (2.5:5.0:92.5, wt/wt) might be useful as an alternative to i.v. injection of CZ for the treatment of acute epileptic seizures. PMID:18720141

  1. Acute morphine affects the rat circadian clock via rhythms of phosphorylated ERK1/2 and GSK3β kinases and Per1 expression in the rat suprachiasmatic nucleus

    PubMed Central

    Pačesová, Dominika; Volfová, Barbora; Červená, Kateřina; Hejnová, Lucie; Novotný, Jiří; Bendová, Zdeňka

    2015-01-01

    Background and Purpose Opioids affect the circadian clock and may change the timing of many physiological processes. This study was undertaken to investigate the daily changes in sensitivity of the circadian pacemaker to an analgesic dose of morphine, and to uncover a possible interplay between circadian and opioid signalling. Experimental Approach A time-dependent effect of morphine (1 mg·kg−1, i.p.) applied either during the day or during the early night was followed, and the levels of phosphorylated ERK1/2, GSK3β, c-Fos and Per genes were assessed by immunohistochemistry and in situ hybridization. The effect of morphine pretreatment on light-induced pERK and c-Fos was examined, and day/night difference in activity of opioid receptors was evaluated by [35S]-GTPγS binding assay. Key Results Morphine stimulated a rise in pERK1/2 and pGSK3β levels in the suprachiasmatic nucleus (SCN) when applied during the day but significantly reduced both kinases when applied during the night. Morphine at night transiently induced Period1 but not Period2 in the SCN and did not attenuate the light-induced level of pERK1/2 and c-Fos in the SCN. The activity of all three principal opioid receptors was high during the day but decreased significantly at night, except for the δ receptor. Finally, we demonstrated daily profiles of pERK1/2 and pGSK3β levels in the rat ventrolateral and dorsomedial SCN. Conclusions and Implications Our data suggest that the phase-shifting effect of opioids may be mediated via post-translational modification of clock proteins by means of activated ERK1/2 and GSK3β. PMID:25828914

  2. Prognosis and treatment of patients with acute alcoholic hepatitis.

    PubMed

    Papastergiou, Vassilios; Burroughs, Andrew K; Tsochatzis, Emmanuel A

    2014-07-01

    Despite alcoholic hepatitis (AH) is the most acute manifestation of alcohol-related liver disease, its treatment remains controversial. Corticosteroids, given either as monotherapy or together with N-acetylecysteine, have been associated with a moderate short-term survival benefit in patients with severe disease. The Maddrey's discriminant function; Glasgow alcoholic hepatitis score; age, bilirubin, INR and creatinine score; and the Model for end-stage liver disease have been proposed for stratifying prognosis in AH enabling selection of the patients to treat. Definition of treatment non-responders using the Lille model after 7 days of therapy may prevent a detrimental impact of prolonged corticosteroids. Pentoxifylline is an effective alternative reducing the occurrence of hepatorenal syndrome. Emerging evidence supports use of liver transplantation in a strictly selected subset of corticosteroid non-responders. PMID:24716632

  3. [RESULTS OF AN ACUTE THROMBOSIS OF HEMORRHOIDAL NODES TREATMENT].

    PubMed

    Akhmedova, E V

    2015-09-01

    The results of treatment of 182 patients, suffering an acute thrombosis of hemorrhoidal nodes of various severity, were studied. In 93 (51.1%) patients (main group) an active surgical tactics was applied. There were conducted urgent, early and postponed operations. In 89 (48.9%) patients (control group) a conservative-expectant tactic was applied. The patients were operated on in terms of 9 - 10 days after admission to hospital. The terms of operation and the method of hemorrhoidectomy were choosed without taking into account the disease severity. Complications in the main group have occurred in 27 (29%) patients, their stationary treatment have lasted 7 - 11 days. In a control group complications were revealed in 27 (30.3%) patients, their stationary stay have lasted from 9 to 28 days. PMID:26817088

  4. Acute methyl salicylate toxicity complicating herbal skin treatment for psoriasis.

    PubMed

    Bell, Anthony J; Duggin, Geoffrey

    2002-06-01

    We present an interesting case of salicylism arising from the use of methyl salicylate as part of a herbal skin cream for the treatment of psoriasis. A 40-year-old man became quite suddenly and acutely unwell after receiving treatment from an unregistered naturopath. Methyl salicylate (Oil of Wintergreen) is widely available in many over the counter topical analgesic preparations and Chinese medicated oils. Transcutaneous absorption of the methyl salicylate was enhanced in this case due to the abnormal areas of skin and use of an occlusive dressing. The presence of tinnitus, vomiting, tachypnoea and typical acid/base disturbance allowed a diagnosis of salicylate toxicity to be made. Our patient had decontaminated his skin prior to presentation, limiting the extent of toxicity and was successfully treated with rehydration and establishment of good urine flow. PMID:12147116

  5. Sinus Node Dysfunction After Acute Lithium Treatment at Therapeutic Levels

    PubMed Central

    Nakatsu, Keigo; Nagamine, Takahiko

    2015-01-01

    Lithium carbonate (lithium) has been used extensively for the treatment of a variety of psychiatric conditions. It requires close monitoring of serum concentration due to its narrow therapeutic window. Cardiac toxicity range from asymptomatic electrocardiographic changes to fatal arrhythmias may occur even at the therapeutic levels. We report a case of psychiatric inpatient who developed asymptomatic severe bradycardia most likely related to sinus node dysfunction due to acute lithium treatment at therapeutic level. After withdrawal of lithium, a time sequential improvement of severe bradycardia examined by repeated electrocardiogram, including Holter monitoring, suggested a relationship between the lithium toxicity and sinus node dysfunction. Other factors such as baseline sinus bradycardia and lower limit of normal thyroid function might be associated with severe bradycardia. This case emphasizes the need, when prescribing lithium, for clinicians to regularly monitor their patients’ electrocardiogram and serum lithium levels to prevent serious or fatal complications, such as cardiac arrest. PMID:27222761

  6. Biology and treatment of adult acute lymphoblastic leukemia.

    PubMed Central

    Levitt, L; Lin, R

    1996-01-01

    The molecular analysis of acute lymphoblastic leukemia (ALL) has provided exciting insights into the pathogenesis of this disease. This disease is heterogenous and can be subtyped based on chromosomal, immunophenotypic, and structural criteria. The varying prognostic implications of different ALL subtypes markedly influence the treatment decisions in adults. Many patients with T-cell ALL can be cured with chemotherapy alone. In contrast, patients with early B-lineage ALL with certain chromosomal abnormalities, especially the Philadelphia chromosome, do not have durable responses to chemotherapy and should receive a bone marrow transplantation if an HLA-matched donor is available. Recent reports have shown improved results for adults with B-cell ALL (Burkitt's) after intensive alternating cycles of chemotherapy containing high doses of methotrexate and cyclophosphamide. Future clinical and laboratory investigation should lead to the development of novel and possibly more effective treatments specifically tailored for different subsets of ALL. PMID:8775728

  7. Family centered brief intensive treatment: a pilot study of an outpatient treatment for acute suicidal ideation.

    PubMed

    Anastasia, Trena T; Humphries-Wadsworth, Terresa; Pepper, Carolyn M; Pearson, Timothy M

    2015-02-01

    Family Centered Brief Intensive Treatment (FC BIT), a hospital diversion treatment program for individuals with acute suicidal ideation, was developed to treat suicidal clients and their families. Individuals who met criteria for hospitalization were treated as outpatients using FC BIT (n = 19) or an intensive outpatient treatment without the family component (IOP; n = 24). Clients receiving FC BIT identified family members or supportive others to participate in therapy. FC BIT clients had significantly greater improvement at the end of treatment compared to IOP clients on measures of depression, hopelessness, and suicidality. Further research is needed to test the efficacy of FC BIT. PMID:25169208

  8. Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions.

    PubMed

    Barrett, D A; Barker, D P; Rutter, N; Pawula, M; Shaw, P N

    1996-06-01

    1. The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants (24-41 weeks gestation) who were given a loading dose of 50 micrograms kg-1 or 200 micrograms kg-1 of diamorphine followed by an intravenous infusion of 15 micrograms kg-1 h-1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2. Following both the 50 micrograms kg-1 or 200 micrograms kg-1 loading doses the mean steady-state plasma concentration (+/- s.d.) of morphine, M3G and M6G were 86 +/- 52 ng ml-1, 703 +/- 400 ng ml-1 and 48 +/- 28 ng ml-1 respectively and morphine clearance was found to be 4.6 +/- 3.2 ml min-1 kg-1. 3. M3G formation clearance was estimated to be 2.5 +/- 1.8 ml min-1 kg-1, and the formation clearance of M6G was estimated to be 0.46 +/- 0.32 ml min-1 kg-1. 4. M3G metabolite clearance was 0.46 +/- 0.60 ml min-1 kg-1, the elimination half-life was 11.1 +/- 11.3 h and the volume of distribution was 0.55 +/- 1.13 l kg-1. M6G metabolite clearance was 0.71 +/- 0.36 ml min-1 kg-1, the elimination half-life was 18.2 +/- 13.6 h and the volume of distribution was 1.03 +/- 0.88 l kg-1. 5. No significant effect of the loading dose (50 micrograms kg-1 or 200 micrograms kg-1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6. We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7. M3G: morphine and M6G: morphine steady-state plasma concentration ratios were 11.0 +/- 10.8 and 0.8 +/- 0.8, respectively. 8. The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults. PMID:8799518

  9. Emerging New Approaches for the Treatment of Acute Promyelocytic Leukemia

    PubMed Central

    Park, Jae; Jurcic, Joseph G.; Rosenblat, Todd; Tallman, Martin S.

    2011-01-01

    The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined with anthracycline-based chemotherapy has revolutionized the prognosis of acute promyelocytic leukemia (APL) with more than 90% complete response rates and cure rates of approximately 80%. The subsequent advent of arsenic trioxide (ATO) in 1990s and progress in the treatment of APL have changed its course from a highly fatal to a highly curable disease. Despite the dramatic improvement in clinical outcome of APL, treatment failure still occurs due most often to early death. Relapse has become increasingly less frequent, most commonly occurring in patients with high-risk disease. A major focus of research for the past decade has been to develop risk-adapted and rationally targeted nonchemotherapy treatment strategies to reduce treatment-related morbidity and mortality to low- and intermediate-risk or older patients while targeting more intensive or alternative therapy to those patients at most risk of relapse. In this review, emerging new approaches to APL treatment with special emhasis on strategies to reduce early deaths, risk-adapted therapy during induction, consolidation and maintenance, as well as an overview of current and future clinical trials in APL will be discussed. PMID:23556100

  10. [The new possibility for the treatment of acute cough].

    PubMed

    Klyachkina, I L

    2015-01-01

    ) can be recommended for the inclusion in the combined treatment of the patients presenting with acute and chronic diseases accompanied by the excretion of viscous and difficult-of-discharge bronchial mucus (such as acute and chronic bronchitis, pneumonia, chronic obstructive pulmonary disease, bronchial asthma with difficulty in sputum discharge, and bronchoectatic disease). PMID:26525480

  11. Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study

    ERIC Educational Resources Information Center

    Kafantaris, Vivian; Coletti, Daniel J.; Dicker, Robert; Padula, Gina; Pleak, Richard R.; Alvir, Jose Ma. J.; Kane, John M.

    2004-01-01

    Objective: There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents. Method: In this discontinuation study, participants received open treatment with lithium at…

  12. [Consensus document on the diagnosis and treatment of acute tonsillopharyngitis].

    PubMed

    Piñeiro Pérez, R; Hijano Bandera, F; Alvez González, F; Fernández Landaluce, A; Silva Rico, J C; Pérez Cánovas, C; Calvo Rey, C; Cilleruelo Ortega, M J

    2011-11-01

    Acute tonsillopharyngitis is one of the most common childhood diseases. Viruses are the most frequent origin. Group A Streptococcus (Streptococcus pyogenes) is the main bacterial cause. A culture or a rapid antigen-detection test of a throat-swab specimen should only be done on the basis of clinical scores, in order to avoid over-diagnosis of bacterial origin and unnecessary antibiotic prescription. The objectives of treatment are: the reduction of symptoms, reduce the contagious period, and prevent local suppurative and systemic complications. Ideally, only confirmed cases should receive antibiotics. If there is no possibility to perform a rapid antigen-detection test, or in some cases if the result is negative, it is recommended to perform a culture and, if there is high suspicious index, to prescribe antibiotics. Penicillin is the treatment of choice, although amoxicillin is also accepted as the first option. Amoxicillin/clavulanate is not indicated in any case as empirical treatment. Macrolides are not a first choice antibiotic, and should be reserved for those patients with immediate penicillin allergy reaction or for the treatment of streptococcal carriers. It is of primordial importance to adapt the prescribing of antibiotics to the scientific evidence. PMID:21920830

  13. Differences in the morphine-induced inhibition of small and large intestinal transit: Involvement of central and peripheral μ-opioid receptors in mice.

    PubMed

    Matsumoto, Kenjiro; Umemoto, Hiroyuki; Mori, Tomohisa; Akatsu, Ryuya; Saito, Shinichiro; Tashima, Kimihito; Shibasaki, Masahiro; Kato, Shinichi; Suzuki, Tsutomu; Horie, Syunji

    2016-01-15

    Constipation is the most common side effect of morphine. Morphine acts centrally and on peripheral sites within the enteric nervous system. There are a few comprehensive studies on morphine-induced constipation in the small and large intestine by the activation of central and peripheral μ-opioid receptors. We investigated the differences in the inhibition of the small and large intestinal transit in normal and morphine-tolerant mice. Morphine reduced the geometric center in the fluorescein isothiocyanate-dextran assay and prolonged the bead expulsion time in a dose-dependent manner. The inhibitory effects of morphine were blocked by μ-opioid antagonist β-funaltrexamine, but not by δ- and κ-opioid antagonists. The peripheral opioid receptor antagonist, naloxone methiodide, partially blocked morphine's effect in the small intestine and completely blocked its effect in the large intestine. The intracerebroventricular administration of naloxone significantly reversed the delay of small intestinal transit but did not affect morphine-induced inhibition of large intestinal transit. Naloxone methiodide completely reversed the inhibition of large intestinal transit in normal and morphine-tolerant mice. Naloxone methiodide partially reversed the morphine-induced inhibition of small intestinal transit in normal mice but completely reversed the effects of morphine in tolerant mice. Chronic treatment with morphine results in tolerance to its inhibitory effect on field-stimulated contraction in the isolated small intestine but not in the large intestine. These results suggest that peripheral and central opioid receptors are involved in morphine-induced constipation in the small and large intestine during the early stage of treatment, but the peripheral receptors mainly regulate constipation during long-term morphine treatment. PMID:26712376

  14. Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction.

    PubMed

    Wu, XuJun; Zhao, Ning; Bai, Fan; Li, ChuanYu; Liu, CiRong; Wei, JingKuan; Zong, Wei; Yang, LiXin; Ryabinin, Andrey E; Ma, YuanYe; Wang, JianHong

    2016-05-01

    Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction

  15. Characterization of the decrease of extracellular striatal dopamine induced by intrastriatal morphine administration

    PubMed Central

    Piepponen, T Petteri; Mikkola, Janne A V; Ruotsalainen, Minna; Jonker, Daniël; Ahtee, Liisa

    1999-01-01

    The effect of intrastriatally-administered morphine on striatal dopamine (DA) release was studied in freely moving rats. Morphine (1, 10 or 100 μM) was given into the striatum by reversed microdialysis, and concentrations of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were simultaneously measured from the striatal dialysates.Intrastriatally-administered morphine significantly and dose-dependently decreased the extracellular concentration of DA, the concentrations of the acidic DA metabolites were only slightly decreased. The effect of morphine was antagonized by naltrexone (2.25 mg kg−1, s.c.). Pretreatment with a preferential κ-opioid receptor antagonist, MR2266 [(−)-5,9 alpha-diethyl-2-(3-furylmethyl)-2′-hydroxy-6,7-benzomorphane; 1 mg kg−1, s.c.], had no effect on the decrease of extracellular DA evoked by intrastriatal morphine (100 μM).Intrastriatal administration of the selective μ-opioid receptor agonist [D-Ala2,MePhe4,Gly-ol5] enkephalin (DAMGO; 1 μM), significantly decreased the extracellular concentration of DA in the striatum.When the rats were given morphine repeatedly in increasing doses (10–25 mg kg−1, s.c.) twice daily for 7 days and withdrawn for 48 h, the decrease of extracellular DA induced by morphine (100 μM) was significantly less than that seen in saline-treated controls.Our results show that besides the well-known stimulatory effect there is a local inhibitory component in the action of morphine on striatal DA release in the terminal regions of nigrostriatal DA neurones. Tolerance develops to this inhibitory effect during repeated morphine treatment. Furthermore, our results suggest that the effect of intrastriatally-administered morphine is mediated by the μ-opioid receptors. PMID:10369482

  16. Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

    PubMed Central

    Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

    2008-01-01

    Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

  17. Severe Acute Axonal Neuropathy following Treatment with Arsenic Trioxide for Acute Promyelocytic Leukemia: a Case Report

    PubMed Central

    Kühn, Marcus; Sammartin, Kety; Nabergoj, Mitja; Vianello, Fabrizio

    2016-01-01

    Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide. PMID:27158436

  18. Sensitivity of quantitative sensory models to morphine analgesia in humans

    PubMed Central

    Olesen, Anne Estrup; Brock, Christina; Sverrisdóttir, Eva; Larsen, Isabelle Myriam; Drewes, Asbjørn Mohr

    2014-01-01

    Introduction Opioid analgesia can be explored with quantitative sensory testing, but most investigations have used models of phasic pain, and such brief stimuli may be limited in the ability to faithfully simulate natural and clinical painful experiences. Therefore, identification of appropriate experimental pain models is critical for our understanding of opioid effects with the potential to improve treatment. Objectives The aim was to explore and compare various pain models to morphine analgesia in healthy volunteers. Methods The study was a double-blind, randomized, two-way crossover study. Thirty-nine healthy participants were included and received morphine 30 mg (2 mg/mL) as oral solution or placebo. To cover both tonic and phasic stimulations, a comprehensive multi-modal, multi-tissue pain-testing program was performed. Results Tonic experimental pain models were sensitive to morphine analgesia compared to placebo: muscle pressure (F=4.87, P=0.03), bone pressure (F=3.98, P=0.05), rectal pressure (F=4.25, P=0.04), and the cold pressor test (F=25.3, P<0.001). Compared to placebo, morphine increased tolerance to muscle stimulation by 14.07%; bone stimulation by 9.72%; rectal mechanical stimulation by 20.40%, and reduced pain reported during the cold pressor test by 9.14%. In contrast, the more phasic experimental pain models were not sensitive to morphine analgesia: skin heat, rectal electrical stimulation, or rectal heat stimulation (all P>0.05). Conclusion Pain models with deep tonic stimulation including C fiber activation and and/or endogenous pain modulation were more sensitive to morphine analgesia. To avoid false negative results in future studies, we recommend inclusion of reproducible tonic pain models in deep tissues, mimicking clinical pain to a higher degree. PMID:25525384

  19. [Acute necrotizing pancreatitis--diagnostic and treatment strategy].

    PubMed

    Madzhov, R; Georgiev, K; Arnaudov, P; Radev, R; Bankov, P

    2003-01-01

    Despite of the current achievements of medicine, the mortality of necrotizing pancreatitis (NP) is still too high--up to 35-40% and stands as a serious diagnostic and treatment problem. The results of treatment of 148 patients, admitted in the clinic with diagnosis NP, 95 males and 53 females, are discussed. The ratio between patients with acute oedematic and acute NP is 81.1% to 18.9%. According to the hystopatology findings, the results are as follows: pancreatic necrosis--128 patients, peripancreatic necrosis--42 patients, retropancreatic necrosis--29 patients, phlegmonous cholecystitis--31 patients. For the exact diagnostic estimation of the development and prognosis of NP, we are based on: Clinic symptomatology, biochemical constellations (the prognostic scale of Ranson), ultrasonography, CT, ERCP, ES, laparoscopy (48 pts), and laparoscopic drainage (34 pts) of the abdominal cavity with one or two drains, in order to decrease the intoxication and manage intraperitoneal irrigation with antibiotics and enzymes. The operative intervations consists of a thorough exploration, broad necrectomy combined with lavage and large drainage. COLD (controlled open lesser sac drainage) has been performed at 34 cases. In 31 pts cholecystectomy and choledochotomy with T-tube drainage of d. choledochus (Kehr drainage) was performed. Reoperations have been made at 34 pts (22.9%); in 11 of them--2 operative revisions have been carried out, in 3 cases--three, and in 3 cases--4 operative revisions were performed. The total postoperative death rate was 21.6% (32 patients). The most common postoperative complications were as follows: pulmonary complications at 11 cases, pleural effusions--9 pts, intraabdominal abscesses--6 patients, postnecrotic pseudocysts--9 cases, pancreatic fistulas--6 cases, fistulas of the colon--2 pts, bleeding--4 patients. PMID:15584453

  20. [Peri-interventional management of acute endovascular stroke treatment].

    PubMed

    Schönenberger, S; Bösel, J

    2015-10-01

    Due to the ground breaking consistent evidence that supports the effect of endovascular stroke treatment (EST), many acute care hospitals and stroke centers will have to be prepared to provide this treatment in an optimal way within the coming years. In addition to the intervention itself, patient preparation, stabilization and monitoring during the treatment as well as the aftercare represent significant challenges and have mostly not yet been sufficiently investigated. Under these aspects, the questions of optimal sedation and airway management have received the highest attention. Based on retrospective study results it already seems to be justified, respecting certain criteria, to prefer EST with the patient under conscious sedation (CS) in comparison to general anesthesia (GA) and to only switch to GA in cases of emergency until this question has been clarified by prospective studies. This and other aspects of peri-interventional management, such as logistics, monitoring, blood pressure, ventilation settings, postprocedural steps of intensive or stroke unit care and imaging follow-up are summarized in this overview. The clinical and radiological selection of patients and thus the decision for intervention or technical aspects of the intervention itself will not be part of this article. PMID:26311331

  1. Plasmapheresis in Acute Fatty Liver of Pregnancy: An Effective Treatment

    PubMed Central

    Seyyed Majidi, Mohammad Reza

    2013-01-01

    Acute fatty liver of pregnancy (AFLP) is an idiopathic disorder with an unknown cause occurring in late pregnancy. The treatment in these patients is often immediate termination of pregnancy, and plasmapheresis provides an effective treatment option. In this paper, we introduce three pregnant women treated with plasmapheresis. The first case was a 22-year-old primigravida woman treated with 22 sessions of plasmapheresis due to AFLP, hepatic and renal failure, coagulopathy, and ventilator-dependent respiratory failure. The second case was a 23-year-old woman in her second pregnancy treated with 4 plasmapheresis sessions due to AFLP, hepatic and renal failure, coagulopathy, and hypoglycemia. The third patient was a 23-year-old primigravida woman treated with 3 plasmapheresis sessions due to AFLP, renal failure, and coagulopathy. Plasmapheresis can be a life-saving treatment in patients with AFLP and is strongly recommended for patients with severity of their disease accompanied by other organ disorders. In addition, shortening the time interval between the termination of pregnancy and initializing plasmapheresis improves the outcome and reduces the duration of hospital stay and sessions of plasmapheresis. PMID:23424692

  2. Evidence for a role of endogenous neurotensin in the development of sensitization to the locomotor stimulant effect of morphine.

    PubMed

    Lévesque, Karine; Lamarche, Caroline; Rompré, Pierre-Paul

    2008-10-10

    This experiment was aimed at exploring the role of endogenous neurotensin in the development of sensitization to the locomotor stimulant effect of morphine. During the induction phase (Days 1, 3, 5 and 7), male Long-Evans adult rats were treated with the neurotensin antagonist SR-48692 (160, 320 or 640 microg/kg, i.p.) or its vehicle, followed by morphine (5.0 mg/kg, i.p.) or its vehicle, and their locomotor activity (ambulatory, non-ambulatory and vertical activity) was measured for 2 h. One week after the last injection, each group received a single injection of morphine (2.5 mg/kg, i.p.) and their locomotor activity was again measured for 2 h (sensitization test, day 14). Results show that SR-48692 alone did not change locomotion. Morphine stimulated locomotor activity, an effect that was stronger on day 7 than on day 1. The two higher doses of SR-48692 attenuated the acute stimulant effect of morphine and prevented the observed increase from day 1 to day 7. The sensitization test on day 14 showed that rats pre-treated with morphine alone displayed significantly stronger ambulatory and vertical activity than vehicle pre-treated rats, a sensitization effect that was attenuated by SR-48692. The present results suggest that endogenous neurotensin contributes to the acute locomotor stimulant effect of morphine and to the induction of its sensitization. PMID:18706409

  3. Treatment of Acute HIV Infection and the Potential Role of Acutely HIV-Infected Persons in Cure Studies.

    PubMed

    Little, Susan J

    Diagnosis of acute HIV infection is important for accurate estimation of HIV incidence, identifying persons who are unaware of their HIV infection, and offering immediate treatment and risk-reduction strategies. The higher viral loads associated with acute HIV infection are associated with an increased risk of transmission. Current treatment recommendations are the same for acute and established infections. Studies of acute HIV infection indicate that initiation of antiretroviral therapy during this period may allow greater recovery of CD4+ T-cell count and function and may result in a smaller latent viral reservoir and a skewing of infection away from central memory CD4+ T cells toward shorter-lived transitional memory CD4+ T cells. This article summarizes a presentation by Susan J. Little, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Los Angeles, California, in April 2015. PMID:27398768

  4. Temperament and Character Dimensions: Correlates of Impulsivity in Morphine Addicts

    PubMed Central

    Abassi, Moslem; Abolghasemi, Abbas

    2015-01-01

    Background: Given the role of temperament and character dimensions on impulsivity in addicts, the purpose of this study was to temperament and character dimensions: correlates of impulsivity in morphine addicts. Objectives: The aim of this study was to determine and verify the association of temperament and character dimensions with impulsivity in morphine addicts. Patients and Methods: The research method was descriptive and correlational. The study sample consisted of 120 morphine addicts referred to drug addiction treatment centers in Ardabil city in 2013. The participants were selected through convenience sampling method from 5 centers. We used impulsivity scale as well as temperament and character inventory to collect data. Results: The results showed that significant relationship existed between impulsivity and characteristics such as novelty seeking, harm avoidance, reward dependence, persistence, self-directedness, and cooperativeness, while no significant relationship between impulsivity and self-transcendence was observed. The results of the multiple regression analysis showed that 47% of the impulsivity variance was explained by temperament and character dimensions. Conclusions: These findings suggest that temperament and character dimensions are associated with impulsivity. The findings also have important implications for prevention, pathology, and treatment in the morphine addicts. PMID:26870706

  5. Morphine mouthwash for the management of oral mucositis in patients with head and neck cancer

    PubMed Central

    Sarvizadeh, Mostafa; Hemati, Simin; Meidani, Mohsen; Ashouri, Moghtada; Roayaei, Mahnaz; Shahsanai, Armindokht

    2015-01-01

    Background: Oral mucositis is a debilitating side effect of cancer treatment for which there is not much successful treatments at yet. We evaluated the effectiveness of topical morphine compared with a routine mouthwash in managing cancer treatment-induced mucositis. Materials and Methods: Thirty head and neck cancer patients with severe mucositis (World Health Organization Grade III or IV) were randomized into the morphine and magic mouthwash groups. Patients received morphine sulfate 2% or magic solution (contained magnesium aluminum hydroxide, viscous lidocaine, and diphenhydramine), 10 ml for every 3 h, six times a day, for 6 days. Both groups received same dietary and oral hygiene instructions and care. Mucositis was graded at baseline and every 3 days after treatment. Patients’ satisfaction and drug effect maintenance were also evaluated. Results: Twenty-eight patients (mean age of 49.5 ± 13.2 years, 63.3% female) completed the trial; 15 in the morphine group and 13 in the magic group. There was a decrease in mucositis severity in both of the morphine (P < 0.001) and magic (P = 0.049) groups. However, at the 6th day, more reduction was observed in mucositis severity in the morphine compared with magic group (P = 0.045). Drug effect maintenance was similar between the two groups, but patients in the morphine group were more satisfied by their treatments than those in the magic group (P = 0.008). Conclusions: Topical morphine is more effective and more satisfactory to patients than the magic mouthwash in reducing severity of cancer treatment-induced oral mucositis. More studies with larger sample size and longer follow-up are required in this regard. PMID:25789270

  6. How assess drugs in the treatment of acute bipolar mania?

    PubMed

    Bourin, Michel; Thibaut, Florence

    2013-01-01

    Bipolar affective disorder is a serious mental disease associated with significant morbidity and mortality. Good-quality research available to guide treatment strategies remains insufficient, particularly with regard to manic or hypomanic episodes. A critical review of the various stages of mania might be helpful for pharmaceutical companies and investigators as a prerequisite for the clinical evaluation of potential antimanic properties of medications. The main difficulty is with a comparison between anticonvulsants, antipsychotics, and mood stabilizers such as lithium (with equal efficacy in the acute phase and the prevention of recurrent manic episodes). No consensus has been reached with regard to the treatment of bouts of acute mania in various parts of the world. Controlled clinical trials have, at last, provided irrefutable evidence of the activity of lithium, which has long been used alone, as well as that of divalproate or its derivatives and, to a lesser extent, carbamazepine. The new antipsychotic agents have more recently established their efficacy, especially aripiprazole, asenapine, quetiapine; olanzapine, risperidone, and ziprasidone (not sure where the paradox is). In Europe, haloperidol is still the reference substance used in clinical trials despite the fact that it is not officially indicated in the treatment of mania. In the USA, lithium, divalproate, or antipsychotics can be prescribed as first-line treatment. In Europe, lithium remains the first-line medication, whereas divalproate and atypical antipsychotic agents are used only as second-line therapy. Although both types of medication (antipsychotics, normothymic agents, and/or anticonvulsants) have proved to be clinically effective in the management of mania by reducing the mania scores overall, the same does not apply, however, to all symptoms of mania. Factorial approaches to mania have all shown that since there are several clinical forms of mania, several clusters of manic symptoms can

  7. New antiplatelet agents in the treatment of acute coronary syndromes.

    PubMed

    Sabouret, Pierre; Taiel-Sartral, Magali

    2014-03-01

    Effective antagonism of the P2Y12 platelet receptor is central to the treatment of acute coronary syndrome (ACS) patients, especially in the setting of percutaneous coronary intervention and stenting. According to consensus guidelines, early revascularization and intensive antiplatelet therapy are key to reducing the complications that arise from myocardial ischaemia and the recurrence of cardiovascular events. Until recently, clopidogrel was the key P2Y12 antagonist advocated, but due to several limitations as an antiplatelet agent, newer drugs with more predictable, rapid and potent effects have been developed. Prasugrel and ticagrelor are now the recommended first-line agents in patients presenting with non-ST-segment elevation ACS and ST-segment elevation ACS, due to large-scale randomized trials that demonstrated net clinical benefit of these agents over clopidogrel, as stated in the European guidelines. Although no study has directly compared the two agents, analysis of the data to date suggests that certain patient types, such as diabetics, those with ST-segment elevation myocardial infarction or renal failure and the elderly may have a better outcome with one agent over the other. Further studies are needed to confirm these differences and answer pending questions regarding the use of these drugs to optimize efficacy while minimizing adverse events, such as bleeding. The aim of this review is to provide an overview of the current P2Y12 receptor antagonists in the treatment of ACS, with a focus on issues of appropriate agent selection, timing of treatment, bleeding risk and the future role of personalized treatment using platelet function and genetic testing. PMID:24630752

  8. Early Prediction of Acute Antidepressant Treatment Response and Remission in Pediatric Major Depressive Disorder

    ERIC Educational Resources Information Center

    Tao, Rongrong; Emslie, Graham; Mayes, Taryn; Nakonezny, Paul; Kennard, Betsy; Hughes, Carroll

    2009-01-01

    The rate of symptom improvement during the early weeks of acute fluoxetine treatment is a good indicator of remission. This finding was made after evaluating the outcome of the fluoxetine treatment on 168 children and adults with depression.

  9. Evaluation of artemisinins for the treatment of acute myeloid leukemia

    PubMed Central

    Drenberg, Christina D.; Buaboonnam, Jassada; Orwick, Shelley J.; Hu, Shuiying; Li, Lie; Fan, Yiping; Shelat, Anang A.; Guy, R. Kiplin; Rubnitz, Jeffrey

    2016-01-01

    Purpose Investigate antileukemic activity of artemisinins, artesunate (ART), and dihydroartemisinin (DHA), in combination with cytarabine, a key component of acute myeloid leukemia (AML) chemotherapy using in vitro and in vivo models. Methods Using ten human AML cell lines, we conducted a high-throughput screen to identify antimalarial agents with antileukemic activity. We evaluated effects of ART and DHA on cell viability, cytotoxicity, apoptosis, lysosomal integrity, and combination effects with cytarabine in cell lines and primary patient blasts. In vivo pharmacokinetic studies and efficacy of single-agent ART or combination with cytarabine were evaluated in three xenograft models. Results ART and DHA had the most potent activity in a panel of AML cell lines, with selectivity toward samples harboring MLL rearrangements and FLT3-ITD mutations. Combination of ART or DHA was synergistic with cytarabine. Single-dose ART (120 mg/kg) produced human equivalent exposures, but multiple dose daily administration required for in vivo efficacy was not tolerated. Combination treatment produced initial regression, but did not prolong survival in vivo. Conclusions The pharmacology of artemisinins is problematic and should be considered in designing AML treatment strategies with currently available agents. Artemisinins with improved pharmacokinetic properties may offer therapeutic benefit in combination with conventional therapeutic strategies in AML. PMID:27125973

  10. Poor survival of treatment-related acute nonlymphocytic leukemia

    SciTech Connect

    Neugut, A.I. Nieves, J.; Murray, T.; Tsai, Weiyann ); Robinson, E. )

    1990-08-29

    Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973-1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6,271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL had an estimated 12-month survival of 10%. The authors conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients.

  11. Outcomes and humanistic issues related to treatment of acute bronchospasm.

    PubMed

    Okamoto, Lynn J

    2006-09-01

    Because of emergency department visits and hospitalizations, the economic costs associated with asthma, chronic obstructive pulmonary disease (COPD), and bronchospasm are a significant portion of total overall treatment costs. A small proportion of patients account for most of the costs, due to disease severity and acute exacerbations. Disease management programs, sponsored by insurance groups and employers, are lowering health and disability costs and reducing days missed from work and school because of exacerbations. Quality-of-life patient assessments are available to assist practitioners in evaluating disease status. Evidenced-based medicine analysis can show that less expensive therapies are not necessarily cost-effective. A study of the rate of hospital admissions from the emergency department showed that although levalbuterol therapy in the emergency department was more costly than racemic albuterol therapy, total overall treatment costs were reduced because of decreased hospitalizations in the levalbuterol-treated patients. Thus, providers, payers, and patients should examine all the scientific evidence (safety, efficacy or effectiveness, economics, and humanistic benefits) to make the most informed health care decision. PMID:16945064

  12. Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats.

    PubMed

    Wallisch, Michael; El Rody, Nehad M; Huang, Baohua; Koop, Dennis R; Baker, James R; Olsen, George D

    2012-01-15

    Respiratory depression is the main obstacle for the safe administration of morphine for acute pain after injury. Due to this complication, new delivery methods are needed to insure that safe and effective doses of opioid analgesics are administered during emergencies. A depot formulation containing a naloxone pro-drug was designed to release the antidote when morphine causes dangerous hypoxic conditions in the blood. The aim of this work was to test the naloxone release in vivo in response to a severe overdose of morphine in the Sprague-Dawley rat model. Non-invasive two-chamber plethysmography was used to monitor and record respiration and to test the capability of the naloxone pro-drug to respond to and rescue morphine-induced respiratory depression in the animal. We show that the pro-drug formulation can both prevent and reverse severe morphine induced respiratory depression. The animal model demonstrates that co-administration of the naloxone pro-drug reliably antagonizes profound respiratory depressive effects of morphine. PMID:22027217

  13. Treatment options for acute uncomplicated cystitis in adults.

    PubMed

    Naber

    2000-08-01

    Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of 10%) of Escherichia coli strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis. PMID:10969048

  14. Treatment options for acute uncomplicated cystitis in adults.

    PubMed

    Naber, K G

    2000-09-01

    Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of < or =10-20%. Otherwise fluoroquinolones are recommended. Alternatives are fosfomycin trometamol or beta-lactams, such as second- or third-generation oral cephalosporins or pivmecillinam, especially when fluoroquinolones are contraindicated or a high proportion (>10%) of Escherichia coil strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis. PMID:11051620

  15. Bergenin decreases the morphine-induced physical dependence via antioxidative activity in mice.

    PubMed

    Yun, Jaesuk; Lee, Yeonju; Yun, Kyunghwa; Oh, Seikwan

    2015-06-01

    Oxidative stress plays a role in the development of physical dependence induced by morphine. Bergenin, a polyphenol found in many Asian, African, and South American medicinal plants, is a potent antinarcotic agent with wide spectrum of pharmacological activities including antioxidant action. In the present study, we observed that bergenin decreased the development of physical dependence induced by morphine in mice and the antioxidant activity of bergenin plays a role in the antinarcotic effects through adapting to morphine-induced oxidative stress in the brain. The naloxone-precipitated withdrawal symptom (jumping frequency) was significantly ameliorated (50% of control group) by administration of bergenin (20 mg/kg) in morphine-treated mice. Furthermore, morphine-induced down-regulation of glutathione (GSH) contents was reversed by bergenin administration in the frontal cortex and liver. Bergenin had no effects on the increased levels of nfr2-dependent antioxidant enzyme HO1 and NQO1 in the frontal cortex, striatum, and liver of morphine-treated mice. However, the morphine-induced increase in nrf2 nuclear translocation in the frontal cortex and striatum was inhibited by bergenin treatment. These results suggest that bergenin has a potential antinarcotic effect via regulation of GSH contents and oxidative stress. PMID:25542428

  16. Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics.

    PubMed

    Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Gray, Andrew; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Howes, John; Weis, Holger; Friedhoff, Lawrence

    2016-08-01

    The aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12-24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours. The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine. PMID:26763764

  17. The effect of Gly-Gln [ß-endorphin30-31] on morphine-evoked serotonin and GABA efflux in the nucleus accumbens of conscious rats.

    PubMed

    Basaran, Nesrin F; Buyukuysal, R Levent; Sertac Yilmaz, M; Aydin, Sami; Cavun, Sinan; Millington, William R

    2016-08-01

    Glycyl-L-glutamine (Gly-Gln; β-endorphin30-31) is an endogenous dipeptide synthesized through the post-translational processing of β-endorphin1-31. Central Gly-Gln administration inhibits the rewarding properties of morphine and attenuates morphine tolerance, dependence and withdrawal although it does not interfere with morphine analgesia. In an earlier study, we found that Gly-Gln inhibits morphine-induced dopamine efflux in the nucleus accumbens (NAc), consistent with its ability to inhibit morphine reward. To further investigate the mechanism responsible for its central effects we tested whether i.c.v. Gly-Gln administration influences the rise in extracellular serotonin and GABA concentrations evoked by morphine in the NAc. Conscious rats were treated with Gly-Gln (100nmol/5μl) or saline i.c.v. followed, 2min later, by morphine (2.5mg/kg) or saline i.p. and extracellular serotonin and GABA concentrations were analyzed by microdialysis and HPLC. Morphine administration increased extracellular serotonin and GABA concentrations significantly within 20min, as shown previously. Unexpectedly, Gly-Gln also increased extracellular serotonin concentrations significantly in control animals. Combined treatment with Gly-Gln+morphine also elevated extracellular serotonin concentrations although the magnitude of the response did not differ significantly from the effect of Gly-Gln or morphine, given alone suggesting that Gly-Gln suppressed morphine induced serotonin efflux. Gly-Gln abolished the morphine-induced rise in extracellular GABA concentrations but had no effect on extracellular GABA when given alone to otherwise untreated animals. These data show that Gly-Gln stimulates NAc serotonin efflux and, together with earlier studies, support the hypothesis that Gly-Gln inhibits the rewarding effects of morphine by modulating morphine induced dopamine, GABA and serotonin efflux in the NAc. PMID:26861257

  18. A new potent analgesic agent with reduced liability to produce morphine tolerance.

    PubMed

    Kiraly, Kornel; Caputi, Francesca Felicia; Hanuska, Adrienn; Kató, Erzsébet; Balogh, Mihaly; Köles, László; Palmisano, Martina; Riba, Pal; Hosztafi, Sándor; Romualdi, Patrizia; Candeletti, Sanzio; Ferdinandy, Péter; Fürst, Susanna; Al-Khrasani, Mahmoud

    2015-08-01

    The therapeutic use of opioids is limited by the development of tolerance to the analgesic effect and the cellular and molecular mechanisms underlying this phenomenon are still not completely understood. For this reason the search for new analgesic derivatives, endowed with lower tolerance, is always an active field. The newly synthesized 14-O-Methylmorphine-6-sulfate (14-O-MeM6SU) shows high efficacy in in vitro assays and a strong analgesic action in the rat tail flick test. The aim of present work was to investigate: the analgesic effect of 14-O-MeM6SU in mouse tail-flick test; the tolerance to analgesic effect of 14-O-MeM6SU compared to morphine in mice, the effects of test compounds on glutamatergic neurotransmission by measuring spontaneous excitatory postsynaptic currents (sEPSCs) of layer V pyramidal cells from rat prefrontal cortices; and the effect of acute and chronic 14-O-MeM6SU treatments on opioid receptor gene expression in SH-SY5Y neuroblastoma cells expressing μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 14-O-MeM6SU was 17 times more potent than morphine in analgesia and had long duration of action in analgesic dose equipotent to morphine. Mice were treated subcutaneously (s.c.) either with 200 μmol/kg morphine or with 14-O-MeM6SU (12 μmol/kg) twice daily for three days. The magnitude of tolerance or cross-tolerance indicated by the shift in antinociceptive ED50 measured was greater for morphine compared to 14-O-MeM6SU. Subsequent to behavioral testing, patch-clamp experiments in layer V pyramidal neurons of rat prefrontal cortical slices in the presence of bicuculline were performed. Both 14-O-MeM6SU (0.1 μM) and morphine (1 μM) decreased the frequency of sEPSCs, indicating reduction of glutamate release. The effect of the novel compound was reversed by the opioid receptor antagonist naloxone, indicating an opioid mediated action. In contrast, the amplitude was not affected. Finally, gene expression data showed a dose

  19. Remifentanil produces cross-desensitization and tolerance with morphine on the mu-opioid receptor.

    PubMed

    Nowoczyn, M; Marie, N; Coulbault, L; Hervault, M; Davis, A; Hanouz, J L; Allouche, S

    2013-10-01

    Remifentanil is a powerful mu-opioid (MOP) receptor agonist used in anaesthesia with a very short half-life. However, per-operative perfusion of remifentanil was shown to increase morphine consumption during post-operative period to relieve pain. In the present study, we aimed to describe the cellular mechanisms responsible for this apparent reduction of morphine efficacy. For this purpose, we first examined the pharmacological properties of both remifentanil and morphine at the MOP receptor, endogenously expressed in the human neuroblastoma SH-SY5Y cell line, to regulate adenylyl cyclase and the MAP kinase ERK1/2 pathway, their potency to promote MOP receptor phosphorylation, arrestin 3-CFP (cyan fluorescent protein) recruitment and receptor trafficking during acute and sustained exposure. In the second part of this work, we studied the effects of a prior exposure of remifentanil on morphine-induced inhibition of cAMP accumulation, activation of ERK1/2 and analgesia. We showed that sustained exposure to remifentanil promoted a rapid desensitization of opioid receptors on both signalling pathways and a pretreatment with this agonist reduced signal transduction produced by a second challenge with morphine. While both opioid agonists promoted Ser(375) phosphorylation on MOP receptor, remifentanil induced a rapid internalization of opioid receptors compared to morphine but without detectable arrestin 3-CFP translocation to the plasma membrane in our experimental conditions. Lastly, a cross-tolerance between remifentanil and morphine was observed in mice using the hot plate test. Our in vitro and in vivo data thus demonstrated that remifentanil produced a rapid desensitization and internalization of the MOP receptor that would reduce the anti-nociceptive effects of morphine. PMID:23792280

  20. Administration of the glial cell modulator, minocycline, in the nucleus accumbens attenuated the maintenance and reinstatement of morphine-seeking behavior.

    PubMed

    Arezoomandan, Reza; Haghparast, Abbas

    2016-03-01

    Relapse to drug use is one of the most difficult clinical problems in treating addiction. Glial activation has been linked with the drug abuse, and the glia modulators such as minocycline can modulate the drug abuse effects. The aim of the present study was to determine whether minocycline could attenuate the maintenance and reinstatement of morphine. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) for 3 days. Following the acquisition of the CPP, the rats were given daily bilateral intra-NAc injections of either minocycline (1, 5, and 10 μg/0.5 μL) or saline (0.5 μL). The animals were tested for conditioning score 60 min after each injection. To induce the reinstatement, a priming dose of morphine (1 mg/kg) was injected 1 day after the final extinction day. The morphine-induced CPP lasted for 7 days after cessation of morphine treatment. Our data revealed that a priming dose of morphine could reinstate the extinguished morphine-induced CPP. Daily intra-accumbal injection of minocycline during the extinction period blocked the maintenance of morphine CPP and also attenuated the priming-induced reinstatement. Our findings indicated that minocycline could facilitate the extinction and attenuate the reinstatement of morphine. These results provided new evidence that minocycline might be considered as a promising therapeutic agent for the treatment of several symptoms associated with morphine abuse. PMID:26745749

  1. Epidural buprenorphine or morphine for the relief of head and neck cancer pain.

    PubMed Central

    Hashimoto, Y.; Utsumi, T.; Tanioka, H.; Rigor, B. M.

    1991-01-01

    We present three cases in which epidural buprenorphine or morphine was used for intractable cancer pain of the head and neck. Excellent pain relief and minimal side effects offered by epidural opioids were of significant benefit. The use of epidural opioids prior to the administration of high doses of oral morphine may be the treatment of choice for pain from malignancy of the head and neck, especially when there is tumor extension or distant metastasis. PMID:1811431

  2. Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions

    PubMed Central

    BARRETT, D. A.; BARKER, D. P.; RUTTER, N.; PAWULA, M.; SHAW, P. N.

    1996-01-01

    1The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants(24–41 weeks gestation) who were given a loading dose of 50 μg kg−1 or 200 μg kg−1 of diamorphine followed by an intravenous infusion of 15 μg kg−1 h−1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2Following both the 50 μg kg−1 or 200 μg kg−1 loading doses the mean steady-state plasma concentration (±s.d.) of morphine, M3G and M6G were 86±52 ng ml−1, 703±400 ng ml−1 and 48±28 ng ml−1 respectively and morphine clearance was found to be 4.6±3.2 ml min−1 kg−1. 3M3G formation clearance was estimated to be 2.5±1.8 ml min−1 kg−1, and the formation clearance of M6G was estimated to be 0.46±0.32 ml min−1 kg−1. 4M3G metabolite clearance was 0.46±0.60 ml min−1 kg−1, the elimination half-life was 11.1±11.3 h and the volume of distribution was 0.55±1.13 l kg−1. M6G metabolite clearance was 0.71±0.36 ml min−1 kg−1, the elimination half-life was 18.2±13.6 h and the volume of distribution was 1.03±0.88 l kg−1. 5No significant effect of the loading dose (50 μg kg−1 or 200 μg kg−1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7M3G:morphine and M6G:morphine steady-state plasma concentration ratios were 11.0±10.8 and 0.8±0.8, respectively. 8The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults. PMID:8799518

  3. Evoked release of methionine enkephalin from tolerant/dependent enteric ganglia: paradoxical dependence on morphine.

    PubMed

    Gintzler, A R; Chan, W C; Glass, J

    1987-04-01

    Experiments were performed in order to determine whether the state of tolerance to and dependence upon opiates is associated with changes in one or more of the characteristics of the electrically induced release of methionine enkephalin from enteric ganglia. Acute morphine pretreatment substantially reduces the magnitude of the evoked release of this peptide from opiate-naive ilea. However, the rate of the evoked release of enkephalin from morphine-pretreated, tolerant/dependent preparations is indistinguishable from that observed for untreated, naive ilea. Paradoxically, 15 min after acute in vitro withdrawal of morphine form such preparations, the presence of morphine appears to be prerequisite for the manifestation of electrically evoked release of methionine enkephalin. The evoked release of this peptide from ilea 60 min after withdrawal is no longer dependent upon morphine. Moreover, the magnitude of the increase in the rate of enkephalin release from these preparations is almost double that observed for opiate-naive ilea. These data indicate that the manifestation of opiate tolerance/dependence for the release of methionine enkephalin from enteric ganglia comprises several adaptive processes, the consequences of which can be observed at different stages of withdrawal. PMID:3470809

  4. Enhanced Sensitivity of α3β4 Nicotinic Receptors in Enteric Neurons after Long-Term Morphine: Implication for Opioid-Induced Constipation.

    PubMed

    Gade, Aravind R; Kang, Minho; Khan, Fayez; Grider, John R; Damaj, M Imad; Dewey, William L; Akbarali, Hamid I

    2016-06-01

    Opioid-induced constipation is a major side effect that persists with long-term opioid use. Previous studies demonstrated that nicotine-induced contractions are enhanced after long-term morphine exposure in guinea pig ileum. In the present study, we examined whether the increased sensitivity to nicotine could be observed in single enteric neurons after long-term morphine exposure, determined the subunits in mouse enteric neurons, and examined the effect of nicotine in reversing opioid-induced constipation. Nicotine (0.03-1 mM) dose-dependently induced inward currents from a holding potential of -60 mV in isolated single enteric neurons from the mouse ileum. The amplitude of the currents, but not the potency to nicotine, was significantly increased in neurons receiving long-term (16-24 h) but not short-term (10 min) exposure to morphine. Quantitative mRNA analysis showed that nicotinic acetylcholine receptor (nAChR) subunit expression in the mouse ileum was α3 ≥ β2 > β4 > α5 > α4 > β3 > α6. Nicotine-induced currents were obtained in neurons from α7, β2, α5, and α6 knockout mice. The currents were, however, inhibited by mecamylamine (10 μM) and the α3β4 blocker α-conotoxin AuIB (3 μM), suggesting that nicotine-induced currents were mediated by the α3β4 subtype of nAChRs on enteric neurons. Conversely, NS3861, a partial agonist at α3β4 nAChR, enhanced fecal pellet expulsion in a dose-dependent manner in mice that received long-term, but not short-term, morphine treatment. Overall, our findings suggest that the efficacy of nAChR agonists on enteric neurons is enhanced after long-term morphine exposure, and activation of the α3β4 subtype of nAChR reverses chronic, but not acute, morphine-induced constipation. PMID:27068812

  5. Activation of p38 signaling in the microglia in the nucleus accumbens contributes to the acquisition and maintenance of morphine-induced conditioned place preference.

    PubMed

    Zhang, Xue-Qin; Cui, Yu; Cui, Yue; Chen, Yu; Na, Xiao-Dong; Chen, Feng-Ying; Wei, Xu-Hong; Li, Yong-Yong; Liu, Xian-Guo; Xin, Wen-Jun

    2012-02-01

    Several lines of evidence have suggested that activated glia contributes to morphine-induced reward (conditioned place preference, CPP). Compared to well-defined roles of astrocyte in morphine CPP, the role of microglia in the nucleus accumbens (NAc) remains poorly characterized. The aim of the present study was to investigate the distinct role of microglia in morphine-induced CPP. Systemic administration of morphine (7.5 mg/kg for 5 days) induced significant preference for the morphine-paired compartment in rats, which lasted for at least 6 days after cessation of morphine treatment. Immunohistochemistry results showed that activation of p38 in the NAc microglia induced by chronic morphine treatment maintained on day 11. Bilateral intra-NAc injection of minocycline, a putative microglia inhibitor, or SB203580, an inhibitor of p38, prior to morphine administration not only inhibited p38 activation in the microglia but impaired the acquisition of CPP. On the day following the acquisition of morphine CPP, a single injection of minocycline or SB203580 failed to block the expression of CPP. Notably, pretreatment with minocycline or SB203580 for 5 days following the acquisition of morphine CPP significantly suppressed the activation of p38 and attenuated the maintenance of morphine CPP. Collectively, our present study indicates that the p38 signaling in the NAc microglia may play an important role in the acquisition and maintenance but not the expression of morphine CPP, and provides new evidence that microglia might be a potential target for the therapy of morphine addiction. PMID:22004988

  6. Technologies for diagnosis and treatment of acute stroke

    SciTech Connect

    Fitch, J.P.

    1998-02-09

    From October 1994 to June 1997, a multidisciplinary team of scientists and engineers at Lawrence Livermore National Laboratory were funded through LDRD to develop and integrate technologies for diagnosis and treatment of acute stroke. The project was summarized in a Science and Technology Review article `Brain Attack` that appeared in June 1997 and again in the Center for Healthcare Technologies Report (UCRL-LR-124761). This article is the best overview of the project, epidemiology of stroke and technical progress. Most of the technical progress has been documented in conference papers and presentations and refereed journal articles. Additional technical publication can be expected as our remaining patent applications progress through the US Patent and Trademark Office. The purpose of this report is to provide an appropriate introduction and organization to the numerous publications so that interested readers can quickly find information. Because there is no documentation for the history of this project, this report provides a summary. It also provides the final status report for the LDRD funding.

  7. Sumatriptan iontophoretic transdermal system for the acute treatment of migraine.

    PubMed

    Vikelis, Michail; Mitsikostas, Dimos D; Rapoport, Alan M

    2014-03-01

    SUMMARY We will describe the pharmacokinetic profile, clinical efficacy and safety data of the sumatriptan iontophoretic transdermal system (Zecuity®, NuPathe Inc., PA, USA), recently approved for the acute treatment of migraine with or without aura in adults, by the US FDA. This transdermal system utilizes a low-level electrical current to deliver sumatriptan transdermally and circumvents the GI tract. Pharmacokinetic studies have shown that iontophoretic delivery of sumatriptan achieves detectable plasma concentrations 15 min after activation with a maximum mean serum concentration of 22 ng/ml. A randomized, double-blind, controlled clinical trial demonstrated minimal triptan-related side effects and superior efficacy versus placebo. The pain-free rate at 2 h postdose was 18% of patients applying the sumatriptan patch versus 9% using the placebo (p = 0.0092). This sumatriptan transdermal system may be a good choice for migraineurs with severe nausea or vomiting, those with intolerable triptan-related adverse events and/or those not responding optimally to oral medications. PMID:24641436

  8. Genetics and Treatments Options for Recurrent Acute and Chronic Pancreatitis

    PubMed Central

    Shelton, Celeste A.; Whitcomb, David C.

    2014-01-01

    Opinion Statement Worldwide research efforts demonstrate a major role of gene-environment interactions for the risk, development, and progression of most pancreatic diseases, including recurrent acute and chronic pancreatitis. New findings of pancreas disease-associated risk variants have been reported in the CPA1, GGT1, CLDN2, MMP1, MTHFR, and other genes. These risk genes and their regulatory regions must be added to the known pathogenic variants in the PRSS1, SPINK1, CFTR, CTRC, CASR, UBR1, SBDS, CEL, and CTSB genes. This new knowledge promises to improve disease management and prevention through personalized medicine. At the same time, however, knowledge of an increasing number of pathogenic variants, and their complicated effects when present in combination, results in increasing difficulty in interpretation and development of recommendations. Direct-to-consumer marketing of genetic testing results also adds complexity to disease management paradigms, especially without interpretation and, in many cases, proven accuracy. While improvements in the ability to rapidly and accurately interpret complex genetic tests are clearly needed, some results, such as pathogenic CFTR variants – including a new class of bicarbonate-defective mutations – and PRSS1 variants have immediate implications that direct management. In addition, discovery of pancreatitis-associated genetic variants in patients with glucose intolerance may suggest underlying type 3c diabetes, which also has implications for treatment and disease management. PMID:24954874

  9. Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD.

    PubMed

    Perfetti, P; Carlier, P; Strada, P; Gualandi, F; Occhini, D; Van Lint, M T; Ibatici, A; Lamparelli, T; Bruno, B; Raiola, A M; Dominietto, A; Di Grazia, C; Bregante, S; Zia, S; Ferrari, G M; Stura, P; Pogliani, E; Bacigalupo, A

    2008-11-01

    Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n=10), III (n=7) or IV (n=6)). The median duration of ECP was 7 months (1-33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day +90 from ECP) (P=0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P=0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P=0.1). A trend for improved survival was seen in grade III-IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease. PMID:18660840

  10. Morphine Tolerance as a Function of Ratio Schedule: Response Requirement or Unit Price?

    ERIC Educational Resources Information Center

    Hughes, Christine; Sigmon, Stacey C.; Pitts, Raymond C.; Dykstra, Linda A.

    2005-01-01

    Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, "l"-methadone, and cocaine dose-dependently decreased…

  11. Effect of Topical Morphine on Cutaneous Leishmaniasis in an Animal Model: A Preliminary Report

    PubMed Central

    Ghaffarpasand, Fariborz; Akbarzadeh, Afsoon; Heiran, Hamid Reza; Karimi, Ali Asghar; Akbarzadeh, Armin; Ghobadifar, Mohamed Amin

    2016-01-01

    Background Pentavalent antimonials remain the choice of treatment for leishmaniasis, despite their toxicity, high cost, and difficult administration. As an alternative, morphine may induce the healing process of cutaneous leishmaniasis by its immunoregulatory characteristics. Objectives To study the effect of morphine on the wound-healing process of cutaneous leishmaniasis (CL) in a mouse model. Materials and Methods This was an experimental study in which 40 BALB/c mice (female, 6 - 8 weeks) were divided into four groups (each n = 10) who received either placebo alone (group 1), morphine ointment after parasite inoculation (group 2), morphine ointment after wound occurrence (group 3), or placebo after wound occurrence (group 4). Wound size was measured weekly for eight weeks. Results On the first day of treatment, the lesions measured ~1.5 mm in diameter. After eight weeks of treatment, the wound size was significantly smaller in the mice who received morphine ointment (4.81 ± 3.22 mm) compared to those who received placebo after parasite inoculation (8.95 ± 5.71 mm; P = 0.0001) or placebo after wound occurrence (P = 0.028). Conclusions The above data suggest that topical application of morphine accelerates the healing process of CL wounds. We are cautiously optimistic that the results of this study can be used clinically for potentiating CL wound-healing. PMID:27437123

  12. Unrecognized acute exertional compartment syndrome of the leg and treatment.

    PubMed

    Popovic, Nebojsa; Bottoni, Craig; Cassidy, Charles

    2011-04-01

    Acute-on-chronic exertional compartment syndrome is rare and may be easily missed without a high degree of awareness and clinical suspicion. We report a case of unrecognized acute-on-chronic exertional compartment syndrome in a recreational soccer player. The late sequela of this condition, foot drop, was successfully treated with transfer of the peroneus longus tendon. PMID:21667742

  13. Morphine Suppresses Tumor Angiogenesis through a HIF-1α/p38MAPK Pathway

    PubMed Central

    Koodie, Lisa; Ramakrishnan, Sundaram; Roy, Sabita

    2010-01-01

    Morphine, a highly potent analgesic agent, is frequently prescribed for moderate to severe cancer pain. In this study, morphine was administered at a clinically relevant analgesic dose to assess tumor cell-induced angiogenesis and subcutaneous tumor growth in nude mice using mouse Lewis lung carcinoma cells (LLCs). Implantation of mice with a continuous slow-release morphine pellet achieved morphine plasma levels within 250–400 ng/ml (measured using a radioimmunoassay, Coat-A-Count Serum Morphine) and was sufficient to significantly reduce tumor cell-induced angiogenesis and tumor growth when compared with placebo treatment. Morphometric analysis for blood vessel formation further confirmed that morphine significantly reduced blood vessel density (P < 0.003), vessel branching (P < 0.05), and vessel length (P < 0.002) when compared with placebo treatment. Morphine’s effect was abolished in mice coadministered the classical opioid receptor antagonist, naltrexone, and in mu-opioid receptor knockout mice, supporting the involvement of the classical opioid receptors in vivo. Morphine’s inhibitory effect is mediated through the suppression of the hypoxia-induced mitochondrial p38 mitogen-activated protein kinase (MAPK) pathway. Our results suggest that in vitro morphine treatment of LLCs inhibits the hypoxia-induced nuclear translocation of hypoxia-inducible transcription factor 1α to reduce vascular endothelial growth factor transcription and secretion, in a manner similar to pharmacological blockade with the p38 MAPK-specific inhibitor, SB203585. These studies indicate that morphine, in addition to its analgesic function, may be exploited for its antiangiogenic potential. PMID:20616349

  14. Sinus Balloon Dilation as Treatment for Acute Sphenoid Sinusitis with Impaired Vision for a Child

    PubMed Central

    Zhao, Yin; Chen, Kangbing; Wang, Zonggui

    2016-01-01

    This paper is about sinus balloon dilatation in treatment of acute left sphenoid sinusitis with left impaired vision in a child. Balloon catheter dilatation (BCD) of the sinus ostia is a new technique. It has been shown to be a minimally invasive technique to manage chronic sinusitis. However, this method is rarely used in the treatment of acute sinusitis. So far, we know of no reported cases of sinus balloon dilatation in treatment of this case, especially for children. PMID:27006660

  15. [Acute poisoning with selected hepatotoxic agents: biochemistry of toxic effect, clinical symptoms and treatment].

    PubMed

    Rusiński, Piotr; Kołaciński, Zbigniew

    2003-01-01

    The paper discusses etiopathogenesis, clinical symptoms and treatment in acute poisoning with hepatotoxic agents. The liver is a critical organ in acute poisoning with Amanita phalloides, carbon tetrachloride, iron compounds and isonicotinic acid hydrazide. Based on literature reports and own experience the authors present the current outlook on the specific treatment of acute poisoning with these xenobiotics. Special consideration was given to biochemical etiopathogenesis of hepatoxicity: oxidative stress, lipid peroxidation and impaired homeostasis of calcium ions and glutathione. Basic principles were also discussed of conservative treatment in hepatic encephalopathy due to toxic liver necrosis. PMID:14569886

  16. Antagonism of κ opioid receptor in the nucleus accumbens prevents the depressive-like behaviors following prolonged morphine abstinence.

    PubMed

    Zan, Gui-Ying; Wang, Qian; Wang, Yu-Jun; Liu, Yao; Hang, Ai; Shu, Xiao-Hong; Liu, Jing-Gen

    2015-09-15

    The association between morphine withdrawal and depressive-like symptoms is well documented, however, the role of dynorphin/κ opioid receptor system and the underlying neural substrates have not been fully understood. In the present study, we found that four weeks morphine abstinence after a chronic escalating morphine regimen significantly induced depressive-like behaviors in mice. Prodynorphin mRNA and protein levels were increased in the nucleus accumbens (NAc) after four weeks of morphine withdrawal. Local injection of κ opioid receptor antagonist nor-Binaltorphimine (norBNI) in the NAc significantly blocked the expression of depressive-like behaviors without influencing general locomotor activity. Thus, the present study extends previous findings by showing that prolonged morphine withdrawal-induced depressive-like behaviors are regulated by dynorphin/κ opioid receptor system, and shed light on the κ opioid receptor antagonists as potential therapeutic agents for the treatment of depressive-like behaviors induced by opiate withdrawal. PMID:26049060

  17. Effects of morphine glucuronides on the function of opioid receptors in human SK-N-SH cells.

    PubMed

    Baker, L; Dye, A; Ratka, A

    2000-03-01

    Morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are active metabolites of morphine. The effects of M3G and M6G on the opioid receptor transduction system has not yet been fully elucidated. Formation of cAMP after treatment with various doses of morphine, M3G, and M6G was studied. M6G and morphine, but not M3G, showed a dose dependent inhibition of cAMP accumulation. Naloxone blocked the inhibitory effect of M6G, M3G, and morphine. Pretreatment with M3G did not change the effects of morphine and M6G. The G-protein inhibitor PTX, prevented morphine, M3G, and M6G effects on cAMP. M3G and M6G vary in their ability to interact with the opioid receptor effector system. Inhibition of cAMP evoked by activation of opioid receptors and inhibitory G-proteins may play a role in the actions of M6G and M3G. PMID:10686401

  18. Effect of Acetaminophen Alone and in Combination with Morphine and Tramadol on the Minimum Alveolar Concentration of Isoflurane in Rats

    PubMed Central

    Chavez, Julio R.; Ibancovichi, José A.; Sanchez-Aparicio, Pedro; Acevedo-Arcique, Carlos M.; Moran-Muñoz, Rafael; Recillas-Morales, Sergio

    2015-01-01

    Background It has been observed that acetaminophen potentiates the analgesic effect of morphine and tramadol in postoperative pain management. Its capacity as an analgesic drug or in combinations thereof to reduce the minimum alveolar concentration (MAC) of inhalational anesthetics represents an objective measure of this effect during general anesthesia. In this study, the effect of acetaminophen with and without morphine or tramadol was evaluated on the isoflurane MAC. Methods Forty-eight male Wistar rats were anesthetized with isoflurane in oxygen. MACISO was determined from alveolar gas samples at the time of tail clamping without the drug, after administering acetaminophen (300 mg/kg), morphine (3 mg/kg), tramadol (10 mg/kg), acetaminophen (300 mg/kg) + morphine (3 mg/kg), and acetaminophen (300 mg/kg) + tramadol (10 mg/kg). Results The control and acetaminophen groups did not present statistically significant differences (p = 0.98). The values determined for MACISO after treatment with acetaminophen + morphine, acetaminophen + tramadol, morphine, and tramadol were 0.98% ± 0.04%, 0.99% ± 0.009%, 0.97% ± 0.02%, and 0.99% ± 0.01%, respectively. Conclusions The administration of acetaminophen did not reduce the MAC of isoflurane and did not potentiate the reduction in MACISO by morphine and tramadol in rats, and therefore does not present a sparing effect of morphine or tramadol in rats anesthetized with isoflurane. PMID:26605541

  19. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury.

    PubMed

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L J; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A; McDevitt, Michael R

    2016-03-23

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)-mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, includingTrp53,Mep1b,Ctr1, andEGFP A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1band fCNT/siTrp53significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  20. Midostaurin: an emerging treatment for acute myeloid leukemia patients

    PubMed Central

    Gallogly, Molly Megan; Lazarus, Hillard M

    2016-01-01

    Acute myeloid leukemia (AML) is a hematologic malignancy that carries a poor prognosis and has garnered few treatment advances in the last few decades. Mutation of the internal tandem duplication (ITD) region of fms-like tyrosine kinase (FLT3) is considered high risk for decreased response and overall survival. Midostaurin is a Type III receptor tyrosine kinase inhibitor found to inhibit FLT3 and other receptor tyrosine kinases, including platelet-derived growth factor receptors, cyclin-dependent kinase 1, src, c-kit, and vascular endothelial growth factor receptor. In preclinical studies, midostaurin exhibited broad-spectrum antitumor activity toward a wide range of tumor xenografts, as well as an FLT3-ITD-driven mouse model of myelodysplastic syndrome (MDS). Midostaurin is orally administered and generally well tolerated as a single agent; hematologic toxicity increases substantially when administered in combination with standard induction chemotherapy. Clinical trials primarily have focused on relapsed/refractory AML and MDS and included single- and combination-agent studies. Administration of midostaurin to relapsed/refractory MDS and AML patients confers a robust anti-blast response sufficient to bridge a minority of patients to transplant. In combination with histone deacetylase inhibitors, responses appear comparable to historic controls, while the addition of midostaurin to standard induction chemotherapy may prolong survival in FLT3-ITD mutant patients. The response of some wild-type (WT)-FLT3 patients to midostaurin therapy is consistent with midostaurin’s ability to inhibit WT-FLT3 in vitro, and also may reflect overexpression of WT-FLT3 in those patients and/or off-target effects such as inhibition of kinases other than FLT3. Midostaurin represents a well-tolerated, easily administered oral agent with the potential to bridge mutant and WT-FLT3 AML patients to transplant and possibly deepen response to induction chemotherapy. Ongoing studies are

  1. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury

    PubMed Central

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J.; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)–mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, including Trp53, Mep1b, Ctr1, and EGFP. A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1b and fCNT/siTrp53 significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  2. Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

    SciTech Connect

    Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L.

    2014-02-15

    Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.

  3. Treatment of acute lateral ankle ligament rupture in the athlete. Conservative versus surgical treatment.

    PubMed

    Lynch, S A; Renström, P A

    1999-01-01

    Acute lateral ankle ligament sprains are common in young athletes (15 to 35 years of age). Diagnostic and treatment protocols vary. Therapies range from cast immobilisation or acute surgical repair to functional rehabilitation. The lateral ligament complex includes 3 capsular ligaments: the anterior tibiofibular (ATFL), calcaneofibular (CFL) and posterior talofibular (PTFL) ligaments. Injuries typically occur during plantar flexion and inversion; the ATFL is most commonly torn. The CFL and the PTFL can also be injured and, after severe inversion, subtalar joint ligaments are also affected. Commonly, an athlete with a lateral ankle ligament sprain reports having 'rolled over' the outside of their ankle. The entire ankle and foot must be examined to ensure there are no other injuries. Clinical stability tests for ligamentous disruption include the anterior drawer test of ATFL function and inversion tilt test of both ATFL and CFL function. Radiographs may rule out treatable fractures in severe injuries or when pain or tenderness are not associated with lateral ligaments. Stress radiographs do not affect treatment. Ankle sprains are classified from grades I to III (mild, moderate or severe). Grade I and II injuries recover quickly with nonoperative management. A non-operative 'functional treatment' programme includes immediate use of RICE (rest, ice, compression, elevation), a short period of immobilisation and protection with a tape or bandage, and early range of motion, weight-bearing and neuromuscular training exercises. Proprioceptive training on a tilt board after 3 to 4 weeks helps improve balance and neuromuscular control of the ankle. Treatment for grade III injuries is more controversial. A comprehensive literature evaluation and meta-analysis showed that early functional treatment provided the fastest recovery of ankle mobility and earliest return to work and physical activity without affecting late mechanical stability. Functional treatment was complication

  4. Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

    PubMed

    Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

    2016-01-01

    Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy. PMID:26817927

  5. Dopamine and 5-HT supersensitivity in nonorganic central pain and in morphine abstinence: fortuitous or renal analogy?

    PubMed

    Sicuteri, F; Anselmi, B; Del Bianco, P L

    1980-01-01

    Unexplained pain, such as central panalgesia, might be the most common clinical expression of a deficiency, central in nature, of the endorphin system. Acute natural opioid deficiency is comparable to morphine withdrawal in addicts characterized by vegetative, psychic disorder and the appearance of pain. An impressive supersensitivity (up to 1000 fold) to dopamine and 5-HT of the smooth muscle (hand dorsal vein: venotest) is detected both in central panalgesia sufferers and in addicts during spontaneous (withdrawal) or pharmacological (naloxone) abstinence. A 5-HT and dopamine supersensitivity, of less intensity, however, (10-30 fold), is found during migraine attacks: on these occasions, morphine-like factors in CSF appear reduced or undetectable, reinforcing the chemical analogy between morphine abstinence and migraine attacks. In the present study, evidence of opiate receptors in the human vein is also provided: 5-HT venospasms, inhibited by morphine, promptly emerge when naloxone is inoculated locally. PMID:7395606

  6. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    SciTech Connect

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E. . E-mail: cng@ohri.ca

    2005-05-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  7. A Pilot Study of Citalopram Treatment in Preventing Relapse of Depressive Episode after Acute Treatment

    PubMed Central

    Cheung, Amy; Levitt, Anthony; Cheng, Michael; Santor, Darcy; Kutcher, Stan; Dubo, Elyse; Jane Garland, E.; Weiss, Margaret; Kiss, Alex

    2016-01-01

    Purpose: To examine the benefit of continuation treatment with citalopram in adolescents 13 to 18 years of age with major depression using a multi-site randomized placebo controlled discontinuation design. Methods: Subjects with depression who responded to open label treatment with citalopram in 12-week acute phase were randomized to continued treatment with citalopram or placebo for 24 weeks. Results: Twenty five subjects were randomized to either continued treatment with citalopram (n = 12) versus placebo (n = 13). Seventy-five percent of subjects on citalopram (75%) remained well as compared to placebo (62%). Time to relapse was compared between groups using the log rank test and was not found to be significantly different (χ2(1) = 0.35, P = 0.55). A Cox proportional hazards model including drug assignment (hazard ratio (HR = 0.51, 95% CI 0.11 to 2.36, P = 0.39), gender (HR = 0.58, 95% CI 0.14 to 2.37, P = 0.44), or HAM-score at entry to continuation phase (HR = 1.33, 95% CI 0.90 to 1.95, P = 0.95) was not significant. Conclusion: Although we did not find statistically significant differences between citalopram and placebo, the findings suggest a possible benefit of continued treatment with citalopram over placebo. A larger clinical trial with adequate power is required to confirm or disconfirm these findings. PMID:27047552

  8. Maternal Depressive Symptoms in Pediatric Major Depressive Disorder: Relationship to Acute Treatment Outcome

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Hughes, Jennifer L.; Stewart, Sunita M.; Mayes, Taryn; Nightingale-Teresi, Jeanne; Tao, Rongrong; Carmody, Thomas; Emslie, Graham J.

    2008-01-01

    A study examined maternal depressive symptoms at the beginning and end of acute pediatric treatment of children with major depressive disorder (MDD). Results suggested a direct and possible reciprocal association between maternal and child depression severity.

  9. Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria.

    PubMed

    Harper, Pauline; Wahlin, Staffan

    2007-12-01

    The porphyrias are a group of uncommon metabolic diseases caused by enzyme deficiencies within heme biosynthesis that lead to neurotoxic or phototoxic heme precursor accumulation. There are four acute porphyrias characterized by neuropsychiatric symptoms: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and 5-aminolevulinic acid dehydratase deficiency porphyria. Treatment includes elimination of any porphyrogenic factor and symptomatic treatment. Carbohydrate and intravenous heme administration constitute specific therapies in the disorders' acute phase. The mainstay treatment in the cutaneous porphyrias is avoidance of sunlight exposure. In porphyria cutanea tarda and the two acute porphyrias with skin manifestations, variegate porphyria and hereditary coproporphyria, care of the vulnerable skin is important. In porphyria cutanea tarda, specific treatment is accomplished by a series of phlebotomies and/or by low-dose chloroquine administration. In erythropoietic protoporphyria, light-protective beta-carotene is prescribed. PMID:18221605

  10. Morphine-induced desensitization and down-regulation at mu-receptors in 7315C pituitary tumor cells

    SciTech Connect

    Puttfarcken, P.S.; Cox, B.M. )

    1989-01-01

    Pituitary 7315c tumor cells maintained in culture were treated with varying concentrations of morphine from 10 nM to 300 {mu}M, for periods of five or forty-eight hours. The ability of the mu-opioid receptor agonist, DAMGO, to inhibit forskolin-stimulated adenylyl cyclase in washed membrane preparations from the treated cells was compared with its activity in membranes from cells incubated in the absence of added morphine. In the same membrane preparations, the number and affinity of mu-opioid receptors was estimated by measurements of ({sup 3}H)diprenorphine binding. After 5 hr of treatment with morphine concentrations of 100 nM or higher, a significant reduction in inhibition of adenylyl cyclase by DAMGO was observed. Little further loss of agonist activity was observed when the incubations were extended to 48 hr. After 5 hr of morphine treatment, there was no change in either the number of receptors, or their affinity for ({sup 3}H)diprenorphine. However after 48 hr of morphine treatment, greater than 25% reductions in receptor number were apparent with morphine pretreatment concentrations of 10 {mu}M or higher. These results suggest that opioid tolerance in this system is primarily associated with a reduced ability of agonist-occupied receptor to activate the effector system. Receptor down-regulation was not necessary for loss of agonist response, although a reduction in receptor number occurred after exposure to high concentrations of morphine for periods longer than 5hr.

  11. Effect of morphine on /sup 3/H-thymidine incorporation in the subependyma of the rat: an autoradiographic study

    SciTech Connect

    Miller, C.R.; O'Steen, W.K.; Deadwyler, S.A.

    1982-06-20

    Following morphine treatment, an autoradiographic study investigated the uptake of /sup 3/H-thymidine by the subependymal cells in the rat brain. /sup 3/H-thymidine was administered subcutaneously to adult, male Sprague-Dawley rats 30 minutes after saline or morphine (19 mg/kg) injection. The animals were sacrified 1 hour after /sup 3/H-thymidine administration. In some experiments the opioid antagonist, naloxone, was given alone 45 minutes before /sup 3/H-thymidine or 125 minutes before morphine treatment. Three areas of the subependyma were evaluated in terms of the percentage labeled cells and number of grains per nucleus, and a dorsal-to-ventral gradiant was described. Morphine treatment significantly increased the number of /sup 3/H-thymidine labeled subependymal cells and number of grains/nucleus within labeled cells. Examination of the distribution of grains/nucleus showed that morphine-treated animals had significantly more cells labeled with 30 or more grains than did saline-injected controls. Prior administration of naloxone blocked the increased /sup 3/H-thymidine uptake in morphine-treated animals but had no significant influence on cell proliferation when administered alone. The data are discussed in terms of morphine's possible dual influence on mechanisms which enhance cell transition from G to S phase and/or which accelerate DNA synthesis once these cells have entered the S phase of cell replication.

  12. Advances in the treatment of acute graft-versus-host disease

    PubMed Central

    Qian, Liren; Wu, Zhengcheng; Shen, Jianliang

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has been widely used for the treatment of hematologic malignant and non-malignant hematologic diseases and other diseases. However, acute graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic transplantation. Acute GVHD may occur in 30% of transplant recipients, which is a syndrome of erythematous skin eruption, cholestatic liver disease and intestinal dysfunction, resulting from the activation of donor T lymphocytes by host antigen-presenting cells, resulting in an immune-mediated inflammatory response. Recent scientific advances in the understanding of the pathogenesis involved in the development of acute GVHD and clinical investigation have provided more effective therapeutic strategies for acute GVHD. This review focuses on major scientific and clinical advances in the treatment of acute GVHD. PMID:23802653

  13. Plasma malondialdehyde levels and opiate withdrawal signs observed in rats treated with morphine plus naloxone: effects of alpha-lipoic acid administration.

    PubMed

    Pinelli, Arnaldo; Cighetti, Giuliana; Trivulzio, Silvio

    2008-08-01

    A number of experimental studies have found that reactive oxygen species are involved during morphine treatment or withdrawal. The aims of this study were to analyse whether morphine administration and/or removal are related to peroxide generation and/or signs of withdrawal in rats, and whether the changes in antioxidant status induced by the administration of an antioxidant may modify peroxide levels and behavioural signs. We injected morphine or morphine and naloxone into rats and evaluated the plasma levels of peroxide malondialdehyde (MDA) and the appearance of withdrawal signs. We also investigated the effects on these parameters induced by the administration of the antioxidant alpha-lipoic acid (LA). Morphine treatment increased MDA levels. Abrupt naloxone-induced morphine withdrawal caused a further and significant increase in MDA, and the appearance of withdrawal signs such as abnormal fecal excretion, shortened latency times and jumping. The administration of LA lowered MDA levels in the rats treated with morphine or morphine plus naloxone, and also decreased MDA values and abstinence signs in the animals treated with morphine plus naloxone. The effects of LA were attributed to its capacity to scavenge peroxides and interfere with the biogenesis of the arachidonic acid metabolites involved in the expression of abstinence symptoms. PMID:18705754

  14. Synthetic substances with morphine-like effect

    PubMed Central

    Braenden, Olav J.; Eddy, Nathan B.; Halbach, H.

    1955-01-01

    For morphine-, morphinan-, pethidine-, methadone-, and dithienyl-butenylamine groups of analgesic compounds a systematic survey is given of how analgesic activity is quantitatively affected by alteration of the chemical constitution. Features common to the structural formulae of substances with morphine-like analgesic effect are pointed out. ImagesFIG. 1FIG. 1(Contd.) PMID:13284565

  15. Expression of BDNF and TrkB Phosphorylation in the Rat Frontal Cortex During Morphine Withdrawal are NO Dependent.

    PubMed

    Peregud, Danil I; Yakovlev, Alexander A; Stepanichev, Mikhail Yu; Onufriev, Mikhail V; Panchenko, Leonid F; Gulyaeva, Natalia V

    2016-08-01

    Nitric oxide (NO) mediates pharmacological effects of opiates including dependence and abstinence. Modulation of NO synthesis during the induction phase of morphine dependence affects manifestations of morphine withdrawal syndrome, though little is known about mechanisms underlying this phenomenon. Neurotrophic and growth factors are involved in neuronal adaptation during opiate dependence. NO-dependent modulation of morphine dependence may be mediated by changes in expression and activity of neurotrophic and/or growth factors in the brain. Here, we studied the effects of NO synthesis inhibition during the induction phase of morphine dependence on the expression of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and insulin-like growth factor 1 (IGF1) as well as their receptors in rat brain regions after spontaneous morphine withdrawal in dependent animals. Morphine dependence in rats was induced within 6 days by 12 injections of morphine in increasing doses (10-100 mg/kg), and NO synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) (10 mg/kg) was given 1 h before each morphine injection. The expression of the BDNF, GDNF, NGF, IGF1, and their receptors in the frontal cortex, striatum, hippocampus, and midbrain was assessed 40 h after morphine withdrawal. L-NAME treatment during morphine intoxication resulted in an aggravation of the spontaneous morphine withdrawal severity. Morphine withdrawal was accompanied by upregulation of BDNF, IGF1, and their receptors TrkB and IGF1R, respectively, on the mRNA level in the frontal cortex, and only BDNF in hippocampus and midbrain. L-NAME administration during morphine intoxication decreased abstinence-induced upregulation of these mRNAs in the frontal cortex, hippocampus and midbrain. L-NAME prevented from abstinence-induced elevation of mature but not pro-form of BDNF polypeptide in the frontal cortex. While morphine abstinence did not affect Trk

  16. Spinal Neuronal NOS Signaling Contributes to Morphine Cardioprotection in Ischemia Reperfusion Injury in Rats.

    PubMed

    Jiang, Lingling; Hu, Jun; He, Shufang; Zhang, Li; Zhang, Ye

    2016-09-01

    Morphine has been widely used as rescue treatment for heart attack and failure in humans for many decades. Relatively little has been known about the role of spinal opioid receptors in morphine cardioprotection. Recent studies have shown that intrathecal injection of morphine can reduce the heart injury caused by ischemia (I)/reperfusion (R) in rats. However, the molecular and cellular mechanisms underlying intrathecal morphine cardioprotection has not been determined. Here, we report that intrathecal morphine postconditioning (IMPOC) rescued mean artery pressure (MAP) and reduced myocardial injury in I/R. Pretreatment with either naloxone (NAL), a selective mu-opioid receptor antagonist, or nitric oxide synthase (NOS) inhibitors via intrathecal delivery completely abolished IMPOC cardioprotection, suggesting that the spinal mu-opioid receptor and its downstream NOS signaling pathway are involved in the mechanism of the morphine-induced effect. Consistent with this, IMPOC significantly enhanced spinal neural NOS phosphorylation, nitric oxide, and cGMP content in a similar time course. Intrathecal application of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific inhibitor of guanylate cyclase, completely ablated IMPOC-induced enhancement of cardioprotection and spinal cGMP content. IMPOC rescue of MAP and ischemic injury is correlated with IMPOC enhancement of NOS signaling. Collectively, these findings strengthen the concept of spinal mu-opioid receptors as a therapeutic target that mediates morphine-induced cardioprotection. We also provide evidence suggesting that the activation of spinal NOS signaling is essential for morphine cardioprotection. PMID:27358482

  17. Brain receptors for thyrotropin releasing hormone in morphine tolerant-dependent rats

    SciTech Connect

    Bhargava, H.N.; Das, S.

    1986-03-01

    The effect of chronic treatment of rats with morphine and its subsequent withdrawal on the brain receptors for thyrotropin releasing hormone (TRH) labeled with /sup 3/H-(3MeHis/sup 2/)TRH (MeTRH). Male Sprague Dawley rats were implanted with 4 morphine pellets (each containing 75 mg morphine base) during a 3-day period. Placebo pellet implanted rats served as controls. Both tolerance to and dependence on morphine developed as a result of this procedure. For characterization of brain TRH receptors, the animals were sacrificed 72 h after the implantation of first pellet. In another set of animals the pellets were removed and were sacrificed 24 h later. The binding of /sup 3/H-MeTRH to membranes prepared from brain without the cerebellum was determined. /sup 3/H-MeTRH bound to brain membranes prepared from placebo pellet implanted rats at a single high affinity site with a B/sub max/ value of 33.50 +/- 0.97 fmol/mg protein and a K/sub d/ of 5.18 +/- 0.21 nM. Implantation of morphine pellets did not alter the B/sub max/ value of /sup 3/H-MeTRH but decreased the K/sub d/ value significantly. Abrupt or naloxone precipitated withdrawal of morphine did not alter B/sub max/ or the K/sub d/ values. The binding of /sup 3/H-MeTRH to brain areas was also determined. The results suggest that the development of tolerance to morphine is associated with enhanced sensitivity of brain TRH receptors, however abrupt withdrawal of morphine does not change the characteristics of brain TRH receptors.

  18. ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults.

    PubMed

    Riddle, Mark S; DuPont, Herbert L; Connor, Bradley A

    2016-05-01

    Acute diarrheal infections are a common health problem globally and among both individuals in the United States and traveling to developing world countries. Multiple modalities including antibiotic and non-antibiotic therapies have been used to address these common infections. Information on treatment, prevention, diagnostics, and the consequences of acute diarrhea infection has emerged and helps to inform clinical management. In this ACG Clinical Guideline, the authors present an evidence-based approach to diagnosis, prevention, and treatment of acute diarrhea infection in both US-based and travel settings. PMID:27068718

  19. The extinction of morphine-induced conditioned place preference by histone deacetylase inhibition.

    PubMed

    Wang, Ru; Zhang, Yan; Qing, Hua; Liu, Mei; Yang, Peng

    2010-10-11

    Recent evidence suggests that epigenetic mechanisms have an important role in the development of addictive behavior. However, little is known about the role of epigenetic mechanisms in the extinction of morphine-induced behavioral changes. In this study, we will examine the effect of histone deacetylase (HDAC) inhibitors on extinction of morphine-induced conditioned place preference (CPP). To facilitate extinction, rats will be administered an HDAC inhibitor (HDACi) following nonreinforced exposure to the conditioned context. To measure persistence, rats were subject to a reinstatement test using 3 mg/kg dose of morphine. To exclude the effect of repeated NaBut injections themselves on morphine-CPP in the absence of extinction session, rats received injection of either NaBut or vehicle for 8 days. We found that HDAC inhibition during nonconfined extinction or confined extinction consolidation can facilitate extinction of morphine-induced CPP. We also showed that the extinction of drug seeking via HDAC inhibition modulates extinction learning such that reinstatement behavior is significantly attenuated. There is no effect of repeated NaBut injections themselves on morphine-CPP in the absence of extinction session. In conclusion, our results extend earlier reports on the ability of HDACi to modify the behavioral effects of drugs of abuse. Our increasing understanding of these epigenetic mechanisms will provide key answers to basic processes in drug addiction and hopefully provide insight into designing improved treatments for drug addiction. PMID:20691756

  20. ROLE OF MENINGEAL MAST CELLS IN INTRATHECAL MORPHINE EVOKED GRANULOMA FORMATION

    PubMed Central

    Yaksh, Tony L.; Allen, Jeffery W.; Veesart, Samantha L.; Horais, Kjersti A; Malkmus, Shelle A.; Scadeng, Miriam; Steinauer, Joanne J.; Rossi, Steve S

    2013-01-01

    Background Intrathecal morphine forms granulomas that arise from the adjacent arachnoid membrane. We propose that these inflammatory cells exit the meningeal vasculature secondary to meningeal mast cell degranulation. Methods Three sets of experiments were accomplished in dogs. 1) Ex vivo Meningeal mast cell degranulation. Histamine release was measured ex vivo from canine dura incubated with opiates. 2) In vivo cutaneous mast cell degranulation. Flare areas on the dog abdomen were measured after subcutaneous opiates. 3) In vivo granuloma pharmacology. Dogs with lumbar intrathecal catheters received infusion of intrathecal saline or intrathecal morphine. Intrathecal morphine dogs received: i) No other treatment (Control); ii) Twice daily subcutaneous naltrexone; iii) Intrathecal co-infusion of cromolyn; or, iv) Twice daily subcutaneous cromolyn for the 24–28 day study course. Results 1) Morphine but not fentanyl evoked dural histamine release, which was blocked by cromolyn but not naloxone. 2) Wheal/flare was produced by subcutaneous morphine, methadone, hydromorphone, but not fentanyl, and was unaffected by naltrexone but prevented by cromolyn. 3) Granulomas occurred in all dogs receiving intrathecal morphine (15/15); subcutaneous naltrexone had no effect on granulomas (6/6), but was reduced by concurrent intrathecal cromolyn (0/5) or twice daily subcutaneous cromolyn (1 of 5). Conclusions The pharmacology of cutaneous/dural MC degranulation and intrathecal granulomas are comparable, not mediated by opioid receptors, and reduced by agents preventing MC degranulation. If an agent produces cutaneous MC degranulation at concentrations produced by intrathecal delivery, the agent may initiate granulomas. PMID:23426209

  1. Modulation of opiate-related signaling molecules in morphine-dependent conditioned behavior: conditioned place preference to morphine induces CREB phosphorylation.

    PubMed

    Morón, José A; Gullapalli, Srinivas; Taylor, Chirisse; Gupta, Achla; Gomes, Ivone; Devi, Lakshmi A

    2010-03-01

    Opiate addiction is a chronic, relapsing behavioral disorder where learned associations that develop between the abused opiate and the environment in which it is consumed are brought about through Pavlovian (classical) conditioning processes. However, the signaling mechanisms/pathways regulating the mechanisms that underlie the responses to opiate-associated cues or the development of sensitization as a consequence of repeated context-independent administration of opiates are unknown. In this study we examined the phosphorylation levels of various classic signaling molecules in brain regions implicated in addictive behaviors after acute and repeated morphine administration. An unbiased place conditioning protocol was used to examine changes in phosphorylation that are associated with (1) the expression of the rewarding effects of morphine and (2) the sensitization that develops to this effect. We also examined the effects of a delta-receptor antagonist on morphine-induced conditioned behavior and on the phosphorylation of classic signaling molecules in view of data showing that blockade of delta-opioid receptor (deltaOR) prevents the development of sensitization to the rewarding effects of morphine. We find that CREB phosphorylation is specifically induced upon the expression of a sensitized response to morphine-induced conditioned behavior in brain areas related to memory consolidation, such as the hippocampus and cortex. A similar effect is also observed, albeit to a lesser extent, in the case of the GluR1 subunit of AMPA glutamate receptor. These increases in the phosphorylation levels of CREB and pGluR1 are significantly blocked by pretreatment with a deltaOR antagonist. These results indicate a critical role for phospho-CREB, AMPA, and deltaOR activities in mediating the expression of a sensitized response to morphine-dependent conditioned behavior. PMID:19956087

  2. Intrathecal morphine for post-thoracotomy pain.

    PubMed

    Gray, J R; Fromme, G A; Nauss, L A; Wang, J K; Ilstrup, D M

    1986-08-01

    We wished to investigate possible differences in the duration of postoperative analgesia and the incidence of respiratory depression after the intrathecal injection in the lumbar area of 10 micrograms/kg morphine in hypobaric and hyperbaric solution for relief of post-thoracotomy pain. Twenty-nine patients received morphine plus dextrose (hyperbaric) and 21 received morphine in preservative-free normal saline. The duration of analgesia was longer with the morphine in the normal saline group than in the hyperbaric group (P less than 0.04). One patient developed delayed respiratory depression. Our data support the use of morphine in normal saline mixtures for greater duration of analgesia after thoracic operations. PMID:3755305

  3. Minocycline prevents morphine-induced apoptosis in rat cerebral cortex and lumbar spinal cord: a possible mechanism for attenuating morphine tolerance.

    PubMed

    Hassanzadeh, Kambiz; Habibi-asl, Bohlool; Farajnia, Safar; Roshangar, Leila

    2011-05-01

    Tolerance to the chronic administration of opioids such as morphine reduces the utility of these drugs in pain management. Despite significant investigation, the precise cellular mechanisms underlying opioid tolerance and dependence remain elusive. It has been indicated that tolerance to the analgesic effect of morphine is associated with apoptosis in the central nervous system. The aim of this study was to examine the effects of the intracerebroventricular (icv) administration of minocycline (a second-generation tetracycline) on morphine-induced apoptosis in the cerebral cortex and lumbar spinal cord of rats after morphine-induced tolerance. Different groups of rats received either morphine (ip) and distilled water (icv) or morphine and different doses of minocycline (icv) or minocycline alone once per day. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to analyze apoptosis. The anti-apoptotic factors, Bcl-2 and HSP 70 and the pro-apoptotic element caspase-3 were evaluated by immunoblotting. The results indicated that minocycline attenuated the number of apoptotic cells in both the cerebral cortex and lumbar spinal cord. Immunoblotting findings showed that the amounts of anti-apoptotic agents (Bcl-2 and HSP 70) were greater in the treatment groups than in the controls in both regions. Although minocycline did not change the level of caspase-3 at the doses used with morphine but the minocycline treated rats showed a significantly lower increase in caspase-3 activity than did in the control. In conclusion, minocycline decreased the number of TUNEL-positive cells and increased the amount of anti-apoptotic factors (Bcl-2 and HSP 70), but did not change the caspase-3 content. PMID:20711699

  4. Morphine modulates doxorubicin uptake and improves efficacy of chemotherapy in an intracranial xenograft model of human glioblastoma.

    PubMed

    da Ros, Martina; Iorio, Anna Lisa; Consolante, Dario; Cardile, Francesco; Muratori, Monica; Fantappiè, Ornella; Lucchesi, Maurizio; Guidi, Milena; Pisano, Claudio; Sardi, Iacopo

    2016-01-01

    Morphine may alter the permeability of Blood-Brain Barrier (BBB), enhancing the access of molecules normally unable to cross it, as Doxorubicin (Dox). In addition, morphine seems to mediate the uptake of Dox into the brain by its reduced efflux mediated by P-glycoprotein (P-gp). We evaluated the antitumor efficacy of Dox plus morphine treatment by an orthotopic glioblastoma xenograft model. Foxn1 mice were injected with U87MG-luc cells in the left lobe of the brain and treated with Dox (5 mg/kg and 2.5 mg/kg, weekly) with or without morphine pretreatment (10 mg/kg, weekly). Bioluminescence imaging (BLI) was used to monitoring tumor growth and response to therapy. Additionally, we investigated the role of morphine on the uptake of Dox by MDCKII cells transfected with human MDR1 gene encoding for P-gp. The data demonstrate that only Dox 5 mg/kg determined a significant tumor regression while the lower dose (2.5 mg/kg) was not effective. However, if combined with morphine, the group treated with Dox 2.5 mg/kg showed a decreasing tumor growth. The average BLI for Dox 2.5 mg/kg plus morphine was 5 fold lower than Dox 2.5 mg/kg alone (P=0.0053) and 8 fold lower than vehicle (P=0.0004). Additionally, Dox increased in MDCKII-P-gp transfected cells only in the presence of morphine with a significantly higher level comparing control group (3.84) vs Dox plus morphine group (12.29, P<0.05). Our results indicate that Dox alone and in combination with morphine appear to be effective in controlling the growth of glioblastoma in a xenograft mouse model. PMID:27152241

  5. Chronic Morphine Alters the Presynaptic Protein Profile: Identification of Novel Molecular Targets Using Proteomics and Network Analysis

    PubMed Central

    Abul-Husn, Noura S.; Annangudi, Suresh P.; Ma'ayan, Avi; Ramos-Ortolaza, Dinah L.; Stockton, Steven D.; Gomes, Ivone; Sweedler, Jonathan V.; Devi, Lakshmi A.

    2011-01-01

    Opiates produce significant and persistent changes in synaptic transmission; knowledge of the proteins involved in these changes may help to understand the molecular mechanisms underlying opiate dependence. Using an integrated quantitative proteomics and systems biology approach, we explored changes in the presynaptic protein profile following a paradigm of chronic morphine administration that leads to the development of dependence. For this, we isolated presynaptic fractions from the striata of rats treated with saline or escalating doses of morphine, and analyzed the proteins in these fractions using differential isotopic labeling. We identified 30 proteins that were significantly altered by morphine and integrated them into a protein-protein interaction (PPI) network representing potential morphine-regulated protein complexes. Graph theory-based analysis of this network revealed clusters of densely connected and functionally related morphine-regulated clusters of proteins. One of the clusters contained molecular chaperones thought to be involved in regulation of neurotransmission. Within this cluster, cysteine-string protein (CSP) and the heat shock protein Hsc70 were downregulated by morphine. Interestingly, Hsp90, a heat shock protein that normally interacts with CSP and Hsc70, was upregulated by morphine. Moreover, treatment with the selective Hsp90 inhibitor, geldanamycin, decreased the somatic signs of naloxone-precipitated morphine withdrawal, suggesting that Hsp90 upregulation at the presynapse plays a role in the expression of morphine dependence. Thus, integration of proteomics, network analysis, and behavioral studies has provided a greater understanding of morphine-induced alterations in synaptic composition, and identified a potential novel therapeutic target for opiate dependence. PMID:22043286

  6. Morphine modulates doxorubicin uptake and improves efficacy of chemotherapy in an intracranial xenograft model of human glioblastoma

    PubMed Central

    da Ros, Martina; Iorio, Anna Lisa; Consolante, Dario; Cardile, Francesco; Muratori, Monica; Fantappiè, Ornella; Lucchesi, Maurizio; Guidi, Milena; Pisano, Claudio; Sardi, Iacopo

    2016-01-01

    Morphine may alter the permeability of Blood-Brain Barrier (BBB), enhancing the access of molecules normally unable to cross it, as Doxorubicin (Dox). In addition, morphine seems to mediate the uptake of Dox into the brain by its reduced efflux mediated by P-glycoprotein (P-gp). We evaluated the antitumor efficacy of Dox plus morphine treatment by an orthotopic glioblastoma xenograft model. Foxn1 mice were injected with U87MG-luc cells in the left lobe of the brain and treated with Dox (5 mg/kg and 2.5 mg/kg, weekly) with or without morphine pretreatment (10 mg/kg, weekly). Bioluminescence imaging (BLI) was used to monitoring tumor growth and response to therapy. Additionally, we investigated the role of morphine on the uptake of Dox by MDCKII cells transfected with human MDR1 gene encoding for P-gp. The data demonstrate that only Dox 5 mg/kg determined a significant tumor regression while the lower dose (2.5 mg/kg) was not effective. However, if combined with morphine, the group treated with Dox 2.5 mg/kg showed a decreasing tumor growth. The average BLI for Dox 2.5 mg/kg plus morphine was 5 fold lower than Dox 2.5 mg/kg alone (P=0.0053) and 8 fold lower than vehicle (P=0.0004). Additionally, Dox increased in MDCKII-P-gp transfected cells only in the presence of morphine with a significantly higher level comparing control group (3.84) vs Dox plus morphine group (12.29, P<0.05). Our results indicate that Dox alone and in combination with morphine appear to be effective in controlling the growth of glioblastoma in a xenograft mouse model. PMID:27152241

  7. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  8. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  9. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  10. Early Treatment of Severe Acute Respiratory Distress Syndrome.

    PubMed

    Przybysz, Thomas M; Heffner, Alan C

    2016-02-01

    Acute respiratory distress syndrome (ARDS) is defined by acute diffuse inflammatory lung injury invoked by a variety of systemic or pulmonary insults. Despite medical progress in management, mortality remains 27% to 45%. Patients with ARDS should be managed with low tidal volume ventilation. Permissive hypercapnea is well tolerated. Conservative fluid strategy can reduce ventilator and hospital days in patients without shock. Prone positioning and neuromuscular blockers reduce mortality in some patients. Early management of ARDS is relevant to emergency medicine. Identifying ARDS patients who should be transferred to an extracorporeal membrane oxygenation center is an important task for emergency providers. PMID:26614238

  11. Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.

    PubMed

    Asher, Alice; Lum, Paula J; Page, Kimberly

    2012-01-01

    Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111

  12. Assessing Candidacy for Acute Hepatitis C Treatment Among Active Young Injection Drug Users: A Case-Series Report

    PubMed Central

    Asher, Alice; Lum, Paula J.; Page, Kimberly

    2011-01-01

    Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All 5 acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. . Establishing treatment candidacy for young IDU in the acute phase involves various health domains. Acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111

  13. Early treatment of hypertension in acute ischemic and intracerebral hemorrhagic stroke: progress achieved, challenges, and perspectives.

    PubMed

    Feldstein, Carlos A

    2014-03-01

    Hypertension is the leading risk factor for ischemic and intracerebral hemorrhagic subtypes of stroke. Additionally, high blood pressure (BP) in the acute cerebrovascular event is associated with poor outcome, and a high percentage of stroke survivors have inadequate control of hypertension. The present is a systematic review of prospective, randomized, and controlled trials carried out on safety and efficacy of antihypertensive treatment of both subtypes of acute stroke. Six trials involving 7512 patients were included, which revealed controversies on the speed and the goals of treatment. These controversies could be due at least in part, from the fact that some studies analyzed the results of antihypertensive treatment in ischemic and intracerebral hemorrhagic subtypes of acute stroke together, and from a different prevalence of past-stroke in the randomized groups. Further research is necessary to establish whether standard antihypertensive treatment provides greater benefit than simple observation in patients with ischemic acute stroke and Stage 2 hypertension of JNC 7, albeit they were not candidates for acute reperfusion. In that case, the target reduction in BP could be 10% to 15% within 24 hours. The recently published INTERACT 2 has provided evidence that patients with hemorrhagic stroke may receive intensive antihypertensive treatment safely with the goal of reducing systolic BP to levels no lower than 130 mm Hg. It is important to take into account that marked BP lowering in acute stroke increases the risk of poor outcome by worsening cerebral ischemia from deterioration of cerebral blood flow autoregulation. PMID:24220549

  14. Degradation of morphine in opium poppy processing waste composting.

    PubMed

    Wang, Yin Quan; Zhang, Jin Lin; Schuchardt, Frank; Wang, Yan

    2014-09-01

    To investigate morphine degradation and optimize turning frequency in opium poppy processing waste composting, a pilot scale windrow composting trial was run for 55 days. Four treatments were designed as without turning (A1), every 5 days turning (A2), every 10 days turning (A3) and every 15 days turning (A4). During composting, a range of physicochemical parameters including the residual morphine degradation, temperature, pH, and the contents of total C, total N, total P and total K were investigated. For all treatments, the residual morphine content decreased below the detection limit and reached the safety standards after day 30 of composting, the longest duration of high temperature (⩾50 °C) was observed in A3, pH increased 16.9-17.54%, total carbon content decreased 15.5-22.5%, C/N ratio reduced from 46 to 26, and the content of total phosphorus and total potassium increased slightly. The final compost obtained by a mixture of all four piles was up to 55.3% of organic matter, 3.3% of total nutrient (N, P2O5 and K2O) and 7.6 of pH. A turning frequency of every ten days for a windrow composting of opium poppy processing waste is recommended to produce homogenous compost. PMID:24613672

  15. The α1 adrenoceptors in ventrolateral orbital cortex contribute to the expression of morphine-induced behavioral sensitization in rats.

    PubMed

    Wei, Lai; Zhu, Yuan-Mei; Zhang, Yu-Xiang; Liang, Feng; Li, Teng; Gao, Hong-Yu; Huo, Fu-Quan; Yan, Chun-Xia

    2016-01-01

    The aim of the present study was to investigate the effect of microinjection of benoxathian, selective α1 adrenoceptor antagonist, into the ventrolateral orbital cortex (VLO) on morphine-induced behavioral sensitization and its underlying molecular mechanism in rats. A single morphine treatment protocol was used in establishing the behavioral sensitization model. The effect of bilateral intra-VLO benoxathian injection on locomotor activity was examined and the protein expression levels of α1 adrenoceptors and activation of extracellular signal-regulated kinase (ERK) in the VLO were detected after locomotor test. The results showed that a single injection of morphine could induce behavioral sensitization by a low challenge dosage of morphine after a 7-days drug free period. Benoxathian significantly suppressed the expression but not the development of morphine-induced behavioral sensitization. Morphine treatment significantly elicited ERK phosphorylation and downregulated the expression level of α1 adrenoceptors in the VLO. In addition, intra-VLO benoxathian injection enhanced the expression levels of α1 adrenoceptors and phosphorylated ERK. These results suggest that α1 adrenoceptors in the VLO are involved in regulating the expression of morphine-induced behavioral sensitization. The effect of decreased locomotor activity by blocking α1 adrenoceptors might be associated with activation of ERK in the VLO. PMID:26520466

  16. Diagnosis and Treatment of Acute Gout at a University Hospital Emergency Department

    PubMed Central

    Schlesinger, Naomi; Radvanski, Diane C; Young, Tina C; McCoy, Jonathan V; Eisenstein, Robert; Moore, Dirk F

    2015-01-01

    Background : Acute gout attacks account for a substantial number of visits to the emergency department (ED). Our aim was to evaluate acute gout diagnosis and treatment at a University Hospital ED. Methods : Our study was a retrospective chart review of consecutive patients with a diagnosis of acute gout seen in the ED 1/01/2004 - 12/31/2010. We documented: demographics, clinical characteristics, medications given, diagnostic tests, consultations and whether patients were hospitalized. Descriptive and summary statistics were performed on all variables. Results : We found 541 unique ED visit records of patients whose discharge diagnosis was acute gout over a 7 year period. 0.13% of ED visits were due to acute gout. The mean patient age was 54; 79% were men. For 118 (22%) this was their first attack. Attack duration was ≤ 3 days in 75%. Lower extremity joints were most commonly affected. Arthrocentesis was performed in 42 (8%) of acute gout ED visits. During 355 (66%) of ED visits, medications were given in the ED and/or prescribed. An anti-inflammatory drug was given during the ED visit during 239 (44%) visits. Medications given during the ED visit included: NSAIDs: 198 (56%): opiates 190 (54%); colchicine 32 (9%) and prednisone 32 (9%). During 154 (28%) visits an anti-inflammatory drug was prescribed. Thirty two (6%) were given no medications during the ED visit nor did they receive a prescription. Acute gout rarely (5%) led to hospitalizations. Conclusion : The diagnosis of acute gout in the ED is commonly clinical and not crystal proven. Anti-inflammatory drugs are the mainstay of treatment in acute gout; yet, during more than 50% of ED visits, anti-inflammatory drugs were not given during the visit. Thus, improvement in the diagnosis and treatment of acute gout in the ED may be required. PMID:26106456

  17. Communication Disorders and Treatment in the Acute Trauma Center Setting.

    ERIC Educational Resources Information Center

    Schwartz-Cowley, Roberta; Stepanik, Mark J.

    1989-01-01

    The Shock Trauma Center of the Maryland Institute for Emergency Medical Services Systems instituted a comprehensive speech-language pathology program to provide acute intervention for communicative disorders in a critical/intensive care environment. This article provides a profile of the Center, a review of communicative impairments, and examples…

  18. Acute Stress Disorder: Conceptual Issues and Treatment Outcomes

    ERIC Educational Resources Information Center

    Koucky, Ellen M.; Galovski, Tara E.; Nixon, Reginald D. V.

    2012-01-01

    Acute stress disorder (ASD) was included as a diagnosis to the 4th edition of the "Diagnostic and Statistical Manual" (American Psychiatric Association, 1994) as a way of describing pathological reactions in the first month following a trauma. Since that time, ASD has been the focus of some controversy, particularly regarding the theoretical basis…

  19. Endovascular Treatment of Acute and Chronic Thoracic Aortic Injury

    SciTech Connect

    Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan

    2007-11-15

    Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.

  20. Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine

    PubMed Central

    Lipton, Richard B.; Fanning, Kristina M.; Serrano, Daniel; Reed, Michael L.; Cady, Roger

    2015-01-01

    Objective: To test the hypothesis that ineffective acute treatment of episodic migraine (EM) is associated with an increased risk for the subsequent onset of chronic migraine (CM). Methods: In the American Migraine Prevalence and Prevention Study, respondents with EM in 2006 who completed the Migraine Treatment Optimization Questionnaire (mTOQ-4) and provided outcome data in 2007 were eligible for analyses. The mTOQ-4 is a validated questionnaire that assesses treatment efficacy based on 4 aspects of response to acute treatment. Total mTOQ-4 scores were used to define categories of acute treatment response: very poor, poor, moderate, and maximum treatment efficacy. Logistic regression models were used to examine the dichotomous outcome of transition from EM in 2006 to CM in 2007 as a function of mTOQ-4 category, adjusting for covariates. Results: Among 5,681 eligible study respondents with EM in 2006, 3.1% progressed to CM in 2007. Only 1.9% of the group with maximum treatment efficacy developed CM. Rates of new-onset CM increased in the moderate treatment efficacy (2.7%), poor treatment efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. In the fully adjusted model, the very poor treatment efficacy group had a more than 2-fold increased risk of new-onset CM (odds ratio = 2.55, 95% confidence interval 1.42–4.61) compared to the maximum treatment efficacy group. Conclusion: Inadequate acute treatment efficacy was associated with an increased risk of new-onset CM over the course of 1 year. Improving acute treatment outcomes might prevent new-onset CM, although reverse causality cannot be excluded. PMID:25609757

  1. 75 FR 32490 - Issues in the Development of Medical Products for the Prophylaxis and/or Treatment of Acute...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... treatment of acute AMR in kidney transplant recipients, including clinical trial design and endpoints. The... acute AMR Endpoints to be evaluated to assess outcome Outcomes achieved with currently used...

  2. Role of prolactin in the modulation of NK and LAK cell activity after short- or long-term morphine administration in neoplastic patients.

    PubMed

    Provinciali, M; Di Stefano, G; Stronati, S; Raffaeli, W; Pari, G; Fabris, N

    1996-10-01

    In a previous work we demonstrated that chronic in vivo antalgic therapy of cancer patients with morphine reduced the endogenous cytotoxic activity of natural killer (NK) cells, while increasing the development of lymphokine activated killer (LAK) cell cytotoxicity. In order to investigate the mechanisms by which morphine affects NK and LAK cell function further, we evaluated the modulation exerted by short- or long-term morphine administration on either NK/LAK cell cytotoxicities or plasma levels of prolactin (PRL) and other immunomodulating neurohormones. An intravenous morphine injection (10 mg) significantly increased the plasma levels of PRL, reduced the cytotoxic activity of NK cells, and increased the development of LAK cell activity 30 min after drug injection in neoplastic patients. The administration of bromocriptine before the injection of morphine prevented both PRL augmentation and the increase in LAK cell activation, although it did not prevent the inhibition of NK cytotoxicity. The chronic oral administration of morphine (90 +/- 30 mg/day for 1 month) also resulted in higher PRL levels; the NK and LAK cell activities were, respectively, lower than or higher than those found in neoplastic patients untreated with morphine. The plasma levels of thyrotropin (TSH), adrenocorticotropic hormone (ACTH) and cortisol were not significantly modified in either short- or long-term experiments. The absolute number and the percentages of lymphocyte populations, as well as the percentage of IL-2 receptors, were not modified after short-term morphine administration whereas little changes of T lymphocyte populations and NK cell number were observed after oral treatment with morphine. In vitro morphine did not affect the development of LAK cell activity. In conclusion, our findings indicate that morphine reduces NK cytotoxicity and increases the development of LAK cell cytotoxicity after short- and long-term administration. The effect of morphine on LAK cell activation

  3. Photoaffinity labeling of opioid receptor with morphine-7,8-oxide (morphine epoxide)

    SciTech Connect

    Takayanagi, I.; Shibata, R.; Miyata, N.; Hirobe, M.

    1982-05-01

    The opioid receptor mediating inhibitory action of morphine in the electrically stimulated guinea pig ileum was irreversibly photoinactivated by morphine epoxide (3 X 10(-6) M). Morphine epoxide (up to 3 X 10(-5) M) did not influence the responses of rat vas deferens (epsilon-receptor) or rabbit vas deferens (kappa-receptor) to electrical stimulation. Effective concentrations of morphine epoxide were much lower in the guinea pig ileum (mu-receptor) than in the mouse vas deference (delta-receptor). The inhibitory action of (Met)-enkephalin on the twitch responses of the rat vas deferens and mouse vas deferens to electrical stimulation were not influenced after irradiation in the presence of morphine epoxide (3 X 10(-6) M). Therefore, morphine epoxide is probably a useful probe for photoaffinity labeling of the mu-receptor in vitro.

  4. [Acute respiratory distress syndrome: definitions, mechanisms and treatment].

    PubMed

    Urso, Domenico Lorenzo

    2006-01-01

    Acute respiratory distress syndrome is a secondary acute respiratory insufficiency caused by an inflammatory syndrome which is characterized by an increased of permeability pulmonary edema, associated with many other clinic anomalies, radiological and pathophysiological not directly caused by, but with which it could coexist, a left atrial hypertension. The illness, characterized by refractory hypoxemia, recognizes several causes, which have direct or indirect harm on the cells of the membrane alveolus-capillary. In spite of the improvements in the therapeutic approach, during these last 40 years, represented by the aid of the mechanical ventilation and the use of selective pulmonary vasodilators, this condition is life threatening and often lethal: 90% of mortality rate amongst those older than 65 years. PMID:16913178

  5. Hepatitis C and recurrent treatment-resistant acute ischemic stroke

    PubMed Central

    Tarsia, Joseph; Dunn, Casey; Aysenne, Aimee; Shah, Basil; Moore, David F.

    2013-01-01

    Since the introduction of recombinant tissue plasminogen activator and thrombolysis, acute ischemic stroke has become a treatable disorder if the patient presents within the 4.5-hour time window. Typically, sporadic stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated with atrial fibrillation. In the over-65-year age group, more rare causes of stroke, such as antiphospholipid syndromes, are unusual; such stroke etiologies are mostly seen in a younger age group (<55 years). Here we describe acute ischemic stroke in three patients >65 years with hepatitis C–associated antiphospholipid antibodies. We suggest that screening for antiphospholipid disorders in the older patient might be warranted, with potential implications for therapeutic management and secondary stroke prevention. PMID:23543984

  6. Hybrid Treatment of Acute Abdominal Aortic Thrombosis Presenting with Paraplegia.

    PubMed

    Azzarone, Matteo; De Troia, Alessandro; Iazzolino, Luigi; Nabulsi, Bilal; Tecchio, Tiziano

    2016-05-01

    Acute thrombotic or embolic occlusion of the abdominal aorta is a rare vascular emergency associated with high morbidity and mortality rates. Classically, the clinical presentation is a severe peripheral ischemia with bilateral leg pain as the predominant feature. Aortic occlusion presenting as an isolated acute onset of paraplegia due to spinal cord ischemia is very rare and requires improved awareness to prevent adverse outcomes associated with delayed diagnosis. We report the case of a 54-year-old man who presented with sudden paraplegia due to the thrombotic occlusion of the infrarenal aorta involving the first segment of the common iliac arteries on both sides; emergent transperitoneal aorto iliac thrombectomy combined with the endovascular iliac kissing-stent technique were performed achieving perioperative complete regression of the symptoms. PMID:26968371

  7. [Invasive diagnosis, transcatheter and surgical treatment of acute coronary syndromes].

    PubMed

    Fabián, J; Hricák, V; Fridrich, V; Fischer, V

    1998-01-01

    On the basis of long-term personal experiences and critical evaluation of the present literatury sources authors described the role of invasive diagnostic methods and transcathetral and cardiosurgical possibilities in the recognition and therapy of acute coronary syndromes. These techniques are, and in the forthcoming year shall be available only in specialized institutions. The paper describes the indication for these aggressive techniques as well as their limitations and complications. The goal of the presented article is to inform both the cardiological and frequently broad physicians' societies about the possibilities of diaventional cardiology and cardiosurgery which will be gradually more applied in the care of the patients with acute coronary syndromes. (Ref. 39, Tab. 2, Fig. 3.) PMID:9919748

  8. Arthroscopic treatment of acute and chronic acromioclavicular joint dislocation.

    PubMed

    Lafosse, Laurent; Baier, Gloria P; Leuzinger, Jan

    2005-08-01

    This article presents an all-arthroscopic technique for coracoclavicular ligament reconstruction by ligamentoplasty after acute or chronic acromioclavicular joint dislocation. A coracoacromial ligament transfer is done to reconstruct the torn coracoclavicular ligaments, similar to open surgery. The coracoacromial ligament is dissected from the undersurface of the acromion and is reinserted on the inferior clavicle by transosseous suture fixation. Additional wire or screw stabilization may be used. With this method, we achieve a very satisfactory reduction of the dislocated acromioclavicular joint. PMID:16086572

  9. Morphine-induced early delays in wound closure: involvement of sensory neuropeptides and modification of neurokinin receptor expression

    PubMed Central

    Rook, Jerri M.; Hasan, Wohaib; McCarson, Kenneth E.

    2014-01-01

    Dose-limiting side effects of centrally-acting opioid drugs have led to the use of topical opioids to reduce the pain associated with chronic cutaneous wounds. However, previous studies indicate that topical morphine application impairs wound healing. This study was designed to elucidate the mechanisms by which morphine delays wound closure. Rats were depleted of sensory neuropeptides by treatment with capsaicin, and full-thickness 4 mm diameter wounds were excised from the intrascapular region. Wounds were treated topically twice daily with 5 mM morphine sulfate, 1 mM substance P, 1 mM neurokinin A, or 5 mM morphine combined with 1 m M substance P or neurokinin A and wound areas assessed. During closure, wound tissue was taken 1, 3, 5, and 8 days post-wounding from control and morphine-treated rats and immunostained for neurokinin receptors and markers for macrophages, myofibroblasts, and vasculature. Results obtained from capsaicin-treated animals demonstrated a significant delay in the early stages of wound contraction that was reversed by neuropeptide application. Treatment of capsaicin-treated rats with topical morphine did not further delay wound closure, suggesting that topical opioids impair wound closure via the inhibition of peripheral neuropeptide release into the healing wound. Morphine application altered neurokinin-1 and neurokinin-2 receptor expression in inflammatory and parenchymal cells essential for wound healing in a cell-specific manner, demonstrating a direct effect of morphine on neurokinin receptor regulation within an array of cells involved in wound healing. These data provide evidence indicating a potentially detrimental effect of topical morphine application on the dynamic wound healing process. PMID:19428329

  10. Holmium:YAG laser angioplasty: treatment of acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Topaz, On

    1993-06-01

    We report our clinical experience with a group of 14 patients who presented with acute myocardial infarction. A holmium:YAG laser was applied to the infarct-related artery. This laser emits 250 - 600 mJ per pulse, with a pulse length of 250 microseconds and repetition rate of 5 Hz. Potential benefits of acute thrombolysis by lasers include the absence of systemic lytic state; a shortened thrombus clearing time relative to using thrombolytics; safe removal of the intracoronary thrombus and facilitation of adjunct balloon angioplasty. Potential clinical difficulties include targeting the obstructive clot and plaque, creation of debris and distal emboli and laser-tissue damage. It is conceivable that holmium:YAG laser can be a successful thrombolytic device as its wave length (2.1 microns) coincides with strong water absorption peaks. Since it is common to find an atherosclerotic plaque located under or distal to the thrombotic occlusion, this laser can also be applied for plaque ablation, and the patient presenting with acute myocardial infarction can clearly benefit from the combined function of this laser system.

  11. Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats.

    PubMed

    Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2016-04-01

    This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a standard environment (SE) or enriched environment (EE) during the development of morphine dependence and withdrawal. Then, rats were tested for withdrawal signs after naloxone injection, anxiety (the elevated plus maze) and depression-related behavior (sucrose preference test), and voluntary consumption of morphine using a two-bottle choice paradigm, in morphine-dependent and morphine-withdrawn rats. The results showed that EE decreased naloxone-precipitated withdrawal signs, but not anxiety or sucrose preference during dependence on morphine. The EE-withdrawn rats showed an increase in the elevated plus maze open arm time and entries and higher levels of sucrose preference than SE rats. Voluntary consumption of morphine was lower in the EE-withdrawn rats than in the SE groups in the second period of drug intake. Thus, exposure to EE reduced the severity of morphine dependence and voluntary consumption of morphine, alongside reductions in anxiety and depression-related behavior in morphine-withdrawn rats. PMID:26397757

  12. Oral Ambulatory Treatment of Acute Osteomyelitis in Children: A Case-Control Study.

    PubMed

    Roul-Levy, Antoine; Looten, Vincent; Bachy, Manon; Grimprel, Emmanuel; Carbajal, Ricardo; Vialle, Raphaël

    2016-03-01

    The treatment of acute hematogenous osteomyelitis has evolved in recent years to a shorter parenteral treatment with an early switch to the oral route. Current publications recommend a 2- to 4-day parenteral treatment before the oral switch. We retrospectively analyzed a series of 45 children aged 1 to 11 years and treated in our department for acute osteomyelitis without severity criterion. Nineteen of 45 patients were treated by an exclusive ambulatory oral treatment by amoxicillin and clavulanic acid. Twenty six of 45 patients had a 2- to 4-day parenteral treatment before the oral switch. The minimum follow-up was 6 months. The primary endpoint was a clinical, radiographic, and biologic healing, 6 months after the beginning of the treatment. The secondary endpoints evaluated were the length of hospitalization, the total duration of treatment, and the type of antibiotic used. On the primary endpoint, we did not find any significant difference between the 2 treatments (P = 0.38). On the duration of treatment, we found a significant difference (P = 0.049) in favor of oral treatment. The ambulatory oral treatment by amoxicillin and clavulanic acid seems to be a valid alternative to the classical parenteral then oral sequence in the treatment of acute hematogenous osteomyelitis in children without severity criterion. PMID:26928094

  13. Can coadministration of oxycodone and morphine produce analgesic synergy in humans? An experimental cold pain study

    PubMed Central

    Grach, Michael; Massalha, Wattan; Pud, Dorit; Adler, Rivka; Eisenberg, Elon

    2004-01-01

    Aims The coadministration of subantinociceptive doses of oxycodone with morphine has recently been shown to result in a synergistic antinociceptive effect in rats. The present study was aimed to investigate the possibility that coadministration of morphine and oxycodone can produce a similar synergistic effect in humans exposed to an experimental model of cold pressor test (CPT). Methods The enriched enrolment design was used to exclude ‘stoic’ and ‘placebo responders’ in a single-blind fashion. ‘Nonstoic’, placebo ‘nonresponder’ female volunteers (n = 30) were randomly assigned to receive 0.5 mg kg−1 oral morphine sulphate, 0.5 mg kg−1 oral oxycodone hydrochloride, and the combination of 0.25 mg kg−1 morphine sulphate with 0.25 mg kg−1 oxycodone hydrochloride, 1 week apart from each other, in a double-blind crossover design. Latency to pain onset (threshold), pain intensity (VAS), and pain tolerance (time until removal of the hand from the water) were measured six times over a 3-h period, subsequent to the administration of each medication, and were used to assess their antinociceptive effect. Results The combination produced a significantly higher effect on latency to pain onset than that of morphine alone [difference in mean postbaseline value 2.2; 95% confidence interval (CI) 0.48, 3.9; P = 0.01] but the effect was nonsignificantly smaller that that of oxycodone alone. Similarly, the effect of the combination on pain tolerance was significantly larger than that of morphine alone (combination difference 8.4; 95% CI 2.5, 14.3; P = 0.007), whereas oxycodone alone caused a nonsignificantly larger effect than that of the combination treatment. Comparisons of pain magnitude failed to show any significant differences between the three treatments. Conclusions These results indicate that at the doses tested, morphine and oxycodone do not produce synergistic antinociceptive effects in healthy humans exposed to the CPT. PMID:15327582

  14. Long-term behavioral effects in a rat model of prolonged postnatal morphine exposure.

    PubMed

    Craig, Michael M; Bajic, Dusica

    2015-10-01

    Prolonged morphine treatment in neonatal pediatric populations is associated with a high incidence of opioid tolerance and dependence. Despite the clinical relevance of this problem, our knowledge of long-term consequences is sparse. The main objective of this study was to investigate whether prolonged morphine administration in a neonatal rat is associated with long-term behavioral changes in adulthood. Newborn animals received either morphine (10 mg/kg) or equal volume of saline subcutaneously twice daily for the first 2 weeks of life. Morphine-treated animals underwent 10 days of morphine weaning to reduce the potential for observable physical signs of withdrawal. Animals were subjected to nonstressful testing (locomotor activity recording and a novel-object recognition test) at a young age (Postnatal Days [PDs] 27-31) or later in adulthood (PDs 55-56), as well as stressful testing (calibrated forceps test, hot plate test, and forced swim test) only in adulthood. Analysis revealed that prolonged neonatal morphine exposure resulted in decreased thermal but not mechanical threshold. Importantly, no differences were found for total locomotor activity (proxy of drug reward/reinforcement behavior), individual forced swim test behaviors (proxy of affective processing), or novel-object recognition test. Performance on the novel-object recognition test was compromised in the morphine-treated group at the young age, but the effect disappeared in adulthood. These novel results provide insight into the long-term consequences of opioid treatment during an early developmental period and suggest long-term neuroplastic differences in sensory processing related to thermal stimuli. PMID:26214209

  15. The Evolution and Current Utility of Esophageal Stent Placement for the Treatment of Acute Esophageal Perforation.

    PubMed

    Herrera, Argenis; Freeman, Richard K

    2016-08-01

    Esophageal stent placement was used primarily for the treatment of malignant strictures until the development of a new generation of biomaterials allowed the production of easily removable, occlusive stents in 2001. Since then, thoracic surgeons have gained experience using esophageal stents for the treatment of acute esophageal perforation. As part of a hybrid treatment strategy, including surgical drainage of infected spaces, enteral nutrition, and aggressive supportive care, esophageal stent placement has produced results that can exceed those of traditional surgical repair. This review summarizes the evolution of esophageal stent use for acute perforation and provides evidence-based recommendations for the technique. PMID:27427525

  16. [Drug treatment of acute myelogenous leukaemia. Current options and future perspectives].

    PubMed

    Telek, Béla; Rejtő, László; Batár, Péter; Miltényi, Zsófia; Reményi, Gyula; Simon, Zsófia; Ujj, Zsófia; Mezei, Gabriella; Szász, Róbert; Kiss, Attila; Udvardy, Miklós; Illés, Árpád

    2016-05-29

    Acute myelogenous leukemia is a heterogeneous disease. Recent molecular mutational analysis techniques have shed more light on different, genetically well characterised types of the disease. Treatment approach is uniform except for acute promyelocytic leukemia. Application of the "3 + 7" induction treatment has been the gold standard in the past 40 years. While the dose of cytarabine has not been changed, escalating daunorubicine dose in younger (<60 years) patients with good performance status to 90 mg/m(2) had a positive impact on overall survival. High dose chemotherapy is tolerated poorly in patients older than 60 years of age and, as treatment is not curative in the elderly, improvement of overall survival and quality of life remains the main goal of management in these patients. Low intensity treatment is beneficial and can provide additional advantage over supportive care. Innovative and targeted therapy approaches might give promise to better management of patients with acute myelogenous leukemia. PMID:27211353

  17. High Feasibility of Empiric HIV Treatment for Patients With Suspected Acute HIV in an Emergency Department.

    PubMed

    Jacobson, Kathleen R; Arora, Sanjay; Walsh, Kristin B; Lora, Meredith; Merjavy, Stephen; Livermore, Shanna; Menchine, Michael

    2016-07-01

    Earlier intervention in acute HIV infection limits HIV reservoirs and may decrease HIV transmission. We developed criteria for empiric antiretroviral therapy (ART) in an emergency department (ED) routine HIV screening program. We assessed the feasibility and willingness of patients with suspected acute HIV infection in the ED to begin ART. A suspected acute HIV infection was defined as a positive HIV antigen antibody combination immunoassay with pending HIV-antibody differentiation test results and HIV RNA viral load. During the study period, there were 16 confirmed cases of acute HIV infection: 11 met our criteria for empiric ART and agreed to treatment, 10 were prescribed ART, and 1 left the ED against medical advice without a prescription for ART. Eight patients completed at least one follow-up visit. Empiric HIV treatment in an ED is feasible, well received by patients, and offers a unique entry point into the HIV care continuum. PMID:27028498

  18. Predictors and Moderators of Acute Outcome in the Treatment for Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    Curry, John; Rohde, Paul; Simons, Anne; Silva, Susan; Vitiello, Benedetto; Kratochvil, Christopher; Reinecke, Mark; Feeny, Norah; Wells, Karen; Pathak, Sanjeev; Weller, Elizabeth; Rosenberg, David; Kennard, Betsy; Robins, Michele; Ginsburg, Golda; March, John

    2006-01-01

    Objective: To identify predictors and moderators of response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive-behavioral therapy (CBT), both fluoxetine and CBT, or clinical management with pill placebo in the Treatment for Adolescents With Depression Study (TADS). Method: Potential baseline…

  19. Clofarabine for the treatment of adult acute lymphoid leukemia: the Group for Research on Adult Acute Lymphoblastic Leukemia intergroup.

    PubMed

    Huguet, Françoise; Leguay, Thibaut; Raffoux, Emmanuel; Rousselot, Philippe; Vey, Norbert; Pigneux, Arnaud; Ifrah, Norbert; Dombret, Hervé

    2015-04-01

    Clofarabine, a second-generation purine analog displaying potent inhibition of DNA synthesis and favorable pharmacologic profile, is approved for the treatment of acute lymphoblastic leukemia (ALL) after failure of at least two previous regimens in patients up to 21 years of age at diagnosis. Good neurologic tolerance, synergy with alkylating agents, management guidelines defined through pediatric ALL and adult acute myeloid leukemia, have also prompted its administration in more than 100 adults with Philadelphia chromosome-positive and negative B lineage and T lineage ALL, as single agent (40 mg/m(2)/ day for 5 days), or in combination. In a Group for Research on Adult Acute Lympho- blastic Leukemia (GRAALL) retrospective study of two regimens (clofarabine ± cyclophosphamide + / - etoposide (ENDEVOL) ± mitoxantrone ± asparaginase ± dexamethasone (VANDEVOL)), remission was achieved in 50% of 55 relapsed/refractory patients, and 17-35% could proceed to allogeneic stem cell. Clofarabine warrants further exploration in advanced ALL treatment and bridge-to-transplant. PMID:24996442

  20. DoD–NCCAM/NIH Workshop on Acupuncture for Treatment of Acute Pain

    PubMed Central

    Belard, Jean Louis; Glowa, John; Khalsa, Partap; Weber, Wendy; Huntley, Kristen

    2013-01-01

    Abstract The Department of Defense (DoD) and the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH) cosponsored a workshop that explored the possible benefits of acupuncture treatment for acute pain. One goal of the workshop was to establish a roadmap to building an evidence base on that would indicate whether acupuncture is helpful for treating active-duty military personnel experiencing acute pain. The workshop highlighted brief presentations on the most current research on acupuncture and acute pain mechanisms. The impact of various modifiers (stress, genetics, population, phenotypes, etc.) on acute pain pathways and response to acupuncture treatment was discussed. Additional presentations focused on common neural mechanisms, an overview of real-world experience with using acupuncture to treat traumatic acute pain, and best tools and methods specific for acupuncture studies. Three breakout groups addressed the gaps, opportunities, and barriers to acupuncture use for acute pain in military and trauma settings. Different models of effectiveness research and optimal research designs for conducting trials in acute traumatic pain were also discussed. PMID:23020611

  1. Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats

    PubMed Central

    Akella, Aparna; Tiwari, Anil K.; Rai, Om P.; Deshpande, Shripad B.

    2016-01-01

    Objective: Pulmonary edema, a manifestation of scorpion envenomation syndrome, is attributed to cardiogenic or noncardiogenic factors. Morphine is a drug used for cardiogenic pulmonary edema and its effect on Mesobuthus tamulus (MBT) venom-induced changes is not known. Therefore, we hypothesized that morphine blocks the MBT venom-induced augmentation of phenyldiguanide (PDG) reflex and pulmonary edema. Materials and Methods: Experiments were performed on anesthetized adult female rats. Trachea and jugular vein were cannulated, and the electrocardiographic potentials were recorded by connecting needle electrodes in limb lead II configuration. PDG (10 ΅g/kg, IV, bolus injection) responses were elicited by bolus injection initially, after saline/morphine (1 mg/kg) and after injecting MBT venom (100 μg/kg). The time-response area of the PDG-induced bradycardiac response after treatment was calculated as % of the initial PDG response area. At the end of experiments, lungs were excised for determination of pulmonary water content. Results: PDG produced bradycardiac response that lasted for >60 s. MBT venom augmented the PDG reflex response by 2.5 times. In morphine pretreated group, augmentation of bradycardiac response induced by MBT venom was absent. MBT venom increased the pulmonary water content, and the increase was absent in morphine pretreated animals. Conclusion: The results reveal that morphine prevents the MBT venom-induced augmentation of PDG reflex response and pulmonary edema. Thus, morphine can be useful in scorpion envenomation syndrome associated with pulmonary edema. PMID:26997727

  2. RACK1 promotes maintenance of morphine-associated memory via activation of an ERK-CREB dependent pathway in hippocampus

    PubMed Central

    Liu, Litao; Zhu, Jiejun; Zhou, Liming; Wan, Lihong

    2016-01-01

    Existence of long-term drug-associated memories may be a crucial factor in drug cravings and relapse. RACK1 plays a critical role in morphine-induced reward. In the present study, we used conditioned place preference (CPP) to assess the acquisition and maintenance of morphine conditioned place preference memory. The hippocampal protein level of RACK1 and synaptic quantitation were evaluated by Western blotting, immunohistochemistry and electron microscopy, respectively. Additionally, shRACK1 (shGnb2l1) was used to silence RACK1 in vivo to evaluate the role and the underlying mechanism of RACK1 in maintenance of morphine CPP memory. We found that morphine induced CPP was maintained for at least 7 days after the last morphine treatment, which indicated a positive correlation with hippocampal RACK1 level, and was accompanied simultaneously by increases in the synapse density and hippocampal expression of synaptophysin (SYP), phosphorylation of extracellular signal-regulated kinase1/2 (pERK1/2) and the phosphorylation of cyclic adenosine monophosphate response element-binding (pCREB). ShGnb2l1 icv injection significantly suppressed the expression of all above proteins, decreased the synapse density in the hippocampus and attenuated the acquisition and maintenance of morphine CPP. Our present study highlights that RACK1 plays an important role in the maintenance of morphine CPP, likely via activation of ERK-CREB pathway in hippocampus. PMID:26830449

  3. Effects of maropitant in cats receiving dexmedetomidine and morphine.

    PubMed

    Martin-Flores, Manuel; Sakai, Daniel M; Learn, McKenzie M; Mastrocco, Alicia; Campoy, Luis; Boesch, Jordyn M; Gleed, Robin D

    2016-06-01

    OBJECTIVE To evaluate the effects of maropitant in cats receiving dexmedetomidine and morphine. DESIGN Randomized controlled trial. ANIMALS 66 healthy female domestic shorthair cats. PROCEDURES Cats were randomly assigned to receive maropitant (1 mg/kg [0.45 mg/lb], SC; maropitant group; n = 32) or saline (0.9% NaCl) solution (0.1 mL/kg [0.045 mL/lb], SC; control group; 34) 20 hours before IM administration of dexmedetomidine (20 μg/kg [9.1 μg/lb]) and morphine (0.1 mg/kg). Following administration of dexmedetomidine and morphine, the incidences of emesis, retching, and signs of nausea (sialorrhea and lip licking) were compared between the 2 groups. The aversive behavioral response of each cat to injection of maropitant or saline solution was scored on a visual analogue scale by each of 4 observers who were unaware of the treatment administered. RESULTS Only 1 of 32 cats in the maropitant group vomited, whereas 20 of 34 control cats vomited. The incidences of emesis and retching for the maropitant group were significantly lower than those for the control group. The incidence of signs of nausea did not differ between the 2 groups. Visual analogue scale scores for the maropitant group were significantly higher than those for the control group. CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study indicated that administration of maropitant to healthy cats approximately 20 hours prior to administration of dexmedetomidine and morphine significantly decreased the incidence of emesis but did not decrease the incidence of signs of nausea. However, maropitant appeared to cause substantial discomfort when injected SC. PMID:27172341

  4. Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice*

    PubMed Central

    Karami, Reza; Hosseini, Mahmoud; Khodabandehloo, Fatimeh; Khatami, Leila; Taiarani, Zahra

    2011-01-01

    Objective: The roles of gonadal hormones and nitric oxide (NO) on the analgesic effects of morphine, tolerance to morphine, and their interactions have been widely investigated. In the present study, the effect of L-arginine (an NO precursor) on morphine tolerance in sham and ovariectomized (OVX) female mice was investigated. Methods: Forty mice were divided into sham and OVX groups. On the first day, a hot plate test ((55±0.2) °C; cut-off 30 s) was carried out as a base record 15 min before injection of morphine (10 mg/kg, subcutaneously (s.c.)) and was repeated every 15 min after injection. The sham group was then divided into two subgroups: sham-tolerance-L-arginine (Sham-Tol-LA) and sham-tolerance-saline (Sham-Tol-Sal) which received either L-arginine 50 mg/kg (intraperitoneally (i.p.)) or saline 10 ml/kg (i.p.), respectively, three times in a day for three consecutive days. Morphine tolerance was induced in animals by injecting 30 mg/kg morphine (s.c.) three times/day for three days. This treatment was also used for OVX subgroups. On the fifth day, the hot plate test was repeated. The analgesic effect of morphine was calculated as the maximal percent effect (MPE). The results were compared using repeated measure analysis of variance (ANOVA). Results: There was no significant difference in MPE between the OVX and sham groups. The MPEs in both the Sham-Tol-Sal and OVX-Tol-Sal groups were lower than those in both the sham and OVX groups (P<0.01). The MPE in the OVX-Tol-Sal group was greater than that in the Sham-Tol-Sal group (P<0.01). The MPE in the Sham-Tol-LA group was higher than that in the Sham-Tol-Sal group (P<0.01). However, there was no significant difference between the Sham-Tol-LA and sham groups or between the OVX-Tol-LA and OVX-Tol-Sal groups. Conclusions: The results of the present study showed that repeated administration of morphine causes tolerance to the analgesic effect of morphine. L-Arginine could prevent tolerance to morphine but its

  5. Historical perspective and contemporary management of acute coronary syndromes: from MONA to THROMBINS2.

    PubMed

    Kline, Kristopher P; Conti, C Richard; Winchester, David E

    2015-01-01

    Acute coronary syndrome (ACS) remains a major burden on morbidity and mortality in the United States. Medical professionals and students often use the mnemonic 'MONA' (morphine, oxygen, nitroglycerin and aspirin) to recall treatments for ACS; however, this list of therapies is outdated. We provide a historical perspective on 'MONA,' attempt to uncover its origin in the medical literature, and demonstrate the myriad changes that have occurred over the last 50 years of ACS management. We have developed a novel mnemonic, 'THROMBINS2' (thienopyridines, heparin/enoxaparin, renin-angiotensin system blockers, oxygen, morphine, beta blocker, intervention, nitroglycerin, statin/salicylate) to help bedside clinicians recall all the elements of contemporary ACS management. We demonstrate the mortality benefit for each component of contemporary ACS management, correlating the continued improvement with historical data on mortality after myocardial infarction. We encourage providers to utilize this mnemonic to explore options and guide treatments in ACS patients. PMID:26457728

  6. A history of chronic morphine exposure during adolescence increases despair-like behaviour and strain-dependently promotes sociability in abstinent adult mice

    PubMed Central

    Lutz, PE; Reiss, D; Ouagazzal, AM; Kieffer, BL

    2013-01-01

    A crucial issue in treating opiate addiction, a chronic relapsing disorder, is to maintain a drug-free abstinent state. Prolonged abstinence associates with mood disorders, strongly contributing to relapse. In particular, substance use disorders occurring during adolescence predispose to depression later in adulthood. Using our established mouse model of opiate abstinence, we characterized emotional consequences into adulthood of morphine exposure during adolescence. Our results indicate that morphine treatment in adolescent mice has no effect on anxiety-like behaviours in adult mice, after abstinence. In contrast, morphine treatment during adolescence increases behavioural despair in adult mice. We also show that morphine exposure strain-dependently enhances sociability in adult mice. Additional research will be required to understand where and how morphine acts during brain maturation to affect emotional and social behaviours into adulthood. PMID:23295400

  7. NUTRITIONAL THERAPY IN THE TREATMENT OF ACUTE CORROSIVE INTOXICATION IN ADULTS

    PubMed Central

    Chibishev, Andon; Markoski, Velo; Smokovski, Ivica; Shikole, Emilija; Stevcevska, Aleksandra

    2016-01-01

    Introduction: Acute intoxications with corrosive substances can cause severe chemical injuries of the upper gastrointestinal tract, most often located in the mouth, pharynx, esophagus, stomach and duodenum. If a patient survives the acute phase of intoxication, regenerative response may result in esophageal and/or gastric stenosis, and increased risk of esophageal and gastric cancer. Such intoxication may be fatal due to perforation or tracheal necrosis. Enteral nutrition is a nutritional method when nutritional substances are administered through specially designed tubing placed through the nose or percutaneously, directly into the GIT. Aim: The aim of this study is to describe the methods of artificial nutrition in patients with acute corrosive intoxications and the importance of nutritional support in the treatment of these intoxications. Discussion: Nutrition in the treatment of acute corrosive intoxications is one of the most important therapeutic processes that largely contribute to faster recovery of the post-corrosive injuries of upper GIT, stabilization of biologic, immunologic and metabolic parameters, and reduction of length of stay in hospital Aim of the treatment of acute corrosive intoxications is to prevent perforation and progressive fibrosis, and esophageal and gastric stenosis. There are different and often conflicting positions, on the conservative treatment of acute corrosive intoxications in adults. Such treatment mainly consists of anti-secretory treatment, antibiotics and intensive hyper-alimentation, aiming to prevent late post-corrosive intoxications. Conclusion: It is considered that nutritional support plays a major role in maintenance of metabolic processes and prevention of severe metabolic complications that could additionally aggravate the condition and impair the treatment. PMID:27047272

  8. Enhanced Extracellular Glutamate and Dopamine in the Ventral Pallidum of Alcohol-Preferring AA and Alcohol-Avoiding ANA Rats after Morphine

    PubMed Central

    Kemppainen, Heidi; Nurmi, Harri; Raivio, Noora; Kiianmaa, Kalervo

    2015-01-01

    The purpose of the present study was to investigate the role of ventral pallidal opioidergic mechanisms in the control of ethanol intake by studying the effects of acute administration of morphine on the levels of GABA, glutamate, and dopamine in the ventral pallidum. The study was conducted using the alcohol-preferring Alko Alcohol (AA) and alcohol-avoiding Alko Non-Alcohol (ANA) rat lines that have well-documented differences in their voluntary ethanol intake and brain opioidergic systems. Therefore, examination of neurobiological differences between the lines is supposed to help to identify the neuronal mechanisms underlying ethanol intake, since selection pressure is assumed gradually to lead to enrichment of alleles promoting high or low ethanol intake, respectively. The effects of an acute dose of morphine (1 or 10 mg/kg s.c.) on the extracellular levels of GABA and glutamate in the ventral pallidum were monitored with in vivo microdialysis. The concentrations of GABA and glutamate in the dialyzates were determined with a high performance liquid chromatography system using fluorescent detection, while electrochemical detection was used for dopamine. The levels of glutamate in the rats injected with morphine 1 mg/kg were significantly above the levels found in the controls and in the rats receiving morphine 10 mg/kg. Morphine 10 mg/kg also increased the levels of dopamine. Morphine could not, however, modify the levels of GABA. The rat lines did not differ in any of the effects of morphine. The data suggest that the glutamatergic and dopaminergic systems in the ventral pallidum may mediate some effects of morphine. Since there were no differences between the AA and ANA lines, the basic hypothesis underlying the use of the genetic animal model suggests that the effects of morphine detected probably do not underlie the different intake of ethanol by the lines and contribute to the control of ethanol intake in these animals. PMID:25653621

  9. Morphine and clonidine combination therapy improves therapeutic window in mice: synergy in antinociceptive but not in sedative or cardiovascular effects.

    PubMed

    Stone, Laura S; German, Jonathan P; Kitto, Kelly F; Fairbanks, Carolyn A; Wilcox, George L

    2014-01-01

    Opioids are used to manage all types of pain including acute, cancer, chronic neuropathic and inflammatory pain. Unfortunately, opioid-related adverse effects such as respiratory depression, tolerance, physical dependence and addiction have led to an underutilization of these compounds for adequate pain relief. One strategy to improve the therapeutic utility of opioids is to co-administer them with other analgesic agents such as agonists acting at α2-adrenergic receptors (α2ARs). Analgesics acting at α2ARs and opioid receptors (ORs) frequently synergize when co-administered in vivo. Multimodal analgesic techniques offer advantages over single drug treatments as synergistic combination therapies produce analgesia at lower doses, thus reducing undesired side effects. This inference presumes, however, that the synergistic interaction is limited to the analgesic effects. In order to test this hypothesis, we examined the effects of α2AR/OR combination therapy in acute antinociception and in the often-undesired side effects of sedation and cardiovascular depression in awake unrestrained mice. Morphine, clonidine or their combination was administered by spinal or systemic injection in awake mice. Antinociception was determined using the warm water tail flick assay (52.5°C). Sedation/motor impairment was evaluated using the accelerating rotarod assay and cardiovascular function was monitored by pulse oximetry. Data were converted to percent maximum possible effect and isobolographic analysis was performed to determine if an interaction was subadditive, additive or synergistic. Synergistic interactions between morphine and clonidine were observed in the antinociceptive but not in the sedative/motor or cardiovascular effects. As a result, the therapeutic window was improved ∼200-fold and antinociception was achieved at non-sedating doses with little to no cardiovascular depression. In addition, combination therapy resulted in greater maximum analgesic efficacy over

  10. Treatment of acute pancreatitis with mexidol and low-intensity laser radiation

    NASA Astrophysics Data System (ADS)

    Parzyan, G. R.; Geinits, A. V.

    2001-04-01

    This article presents the results of treatment of 54 patients with acute pancreatitis. The patients were divided into two groups according to the method of treatment. The control group (26 patients) received a conventional therapy, whereas the experimental group (28 patients) received mexidol in combination with the intravenous laser irradiation of blood. Clinical and laboratory tests confirmed a high efficiency of the combined therapy based on the administration of mexidol antioxidant and low-intensity (lambda) equals 0.63 micrometers diode laser irradiation of blood. This therapeutic technique produced an influence on the basic pathogenetic mechanisms of acute pancreatitis. The application of this method of treatment improved the course and prognosis of acute pancreatitis.

  11. Effect of Early Statin Treatment in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

    PubMed Central

    Sim, Doo Sun; Cho, Kyung Hoon; Ahn, Youngkeun; Kim, Young Jo; Chae, Shung Chull; Hong, Taek Jong; Seong, In Whan; Chae, Jei Keon; Kim, Chong Jin; Cho, Myeong Chan; Rha, Seung-Woon; Bae, Jang Ho; Seung, Ki Bae; Park, Seung Jung

    2013-01-01

    Background and Objectives The benefit of early statin treatment following acute myocardial infarction (MI) complicated with cardiogenic shock (CS) has not been well studied. We sought to assess the effect of early statin therapy in patients with CS complicating acute MI. Subjects and Methods We studied 553 statin-naive patients with acute MI and CS (Killip class IV) who underwent revascularization therapy between November 2005 and January 2008 at 51 hospitals in the Korea Acute Myocardial Infarction Registry. Patients were divided into 2 groups: those who received statins during hospitalization (n=280) and those who did not (n=273). The influence of statin treatment on a 12-month clinical outcome was examined using a matched-pairs analysis (n=200 in each group) based on the propensity for receiving statin therapy during hospitalization. Results Before adjustment, patients receiving statin, compared to those not receiving statin, had a more favorable clinical profile, were less likely to suffer procedural complications, and more likely to receive adequate medical therapy. Patients receiving statin had lower unadjusted in-hospital mortality and composite rate of mortality, MI, and repeat revascularization at 12 months, which remained significantly lower after adjustment for patient risk, procedural characteristics, and treatment propensity. Conclusion In CS patients with acute MI undergoing revascularization therapy, early statin treatment initiated during hospitalization was associated with lower rates of in-hospital death and 12-month adverse cardiac events. PMID:23508129

  12. Divergent Effect of Dezocine, Morphine and Sufentanil on Intestinal Motor Function in Rats

    PubMed Central

    Bian, Xiaocui; Zhou, Renlong; Yang, Yuting; Li, Peiying; Hang, Yannan; Hu, Youmin; Yang, Liqun; Wen, Daxiang

    2015-01-01

    Background: Opioid induced bowel dysfunction is the most common side effect of preoperatively administrated morphine, fentanyl and its derivative. However, the influence of dezocine on intestinal mobility is rarely reported. This study was designed to investigate the effects of dezocine, morphine and sufentanil on both intestinal smooth muscle contraction and propulsion in rats. Methods: Contractile tension and frequency of isolated rat small intestine smooth muscle were measured using tension transducer after incubation with different concentrations of dezocine, morphine and sufentanil. The propulsive rate of methylene blue in rat intestinal tract was measured 30 minutes after intraperitoneal injection of morphine, sufentanil and dezocine. Percent of change in contractile tension and contraction frequency compared to baseline level were calculated to evaluate muscle contraction. Propulsive rate of methylene blue was calculated as the percentage of methylene blue moving distance in intestinal tract compared to the length of the small intestine. Results: Morphine and sufentanil significantly increased the contractile tension of isolated small intestine smooth muscle at high doses. The contraction frequency did not change significantly among the 3 tested doses. Increasing the dose of dezocine from 1.7 mg.L-1 to 10.2 mg.L-1 did not change either the contractile tension or the contraction frequency. The propulsive rate of methylene blue in intestinal tract was significantly decreased after the treatment with morphine, sufentanil and dezocine (45.6%, 43.7%, and 42.1% respectively) compared to control group(57.1%), while the difference among the 3 drug groups were not significant. Conclusion: Morphine and sufentanil may dose dependently increase the contractile tension and contraction ability of isolated rat small intestine smooth muscle, while dezocine has no significant effect on intestine smooth muscle contraction. However, all these opioids might impair small

  13. Successful treatment of pegaspargase-induced acute hepatotoxicity with vitamin B complex and L-carnitine

    PubMed Central

    Karur, Vinit; Herrington, Jon D.; Walker, Mary G.

    2016-01-01

    Pegaspargase is a chemotherapy drug used in the treatment of acute lymphoblastic leukemia (ALL). One of the adverse effects of pegaspargase is hepatotoxicity, which can rapidly lead to liver failure and death. We report a patient with ALL who developed pegaspargase-induced severe hepatotoxicity that was rescued by treatment with vitamin B complex and L-carnitine. Our patient had a quicker response than prior reported cases, suggesting this treatment might be a better regimen. PMID:26722167

  14. Treatment of compartment syndrome of the thigh associated with acute renal failure after the Wenchuan earthquake.

    PubMed

    Duan, Xin; Zhang, Kaiwei; Zhong, Gang; Cen, Shiqiang; Huang, Fuguo; Lv, Jingtong; Xiang, Zhou

    2012-04-01

    Compartment syndrome of the thigh is a rare emergency often treated operatively. The purpose of this study was to evaluate the effects of nonoperative treatment for compartment syndrome of the thigh associated with acute renal failure after the 2008 Wenchuan earthquake. Nonoperative treatment, which primarily involves continuous renal replacement therapy, was performed in 6 patients (3 men and 3 women) who presented with compartment syndrome of the thigh associated with acute renal failure. The mean mangled extremity severity score (MESS) and laboratory data regarding renal function were analyzed before and after treatment, and the clinical outcome was evaluated at 17-month follow-up. Laboratory data regarding renal function showed improvements. All 6 patients survived with the affected lower limbs intact after nonoperative treatment. Follow-up revealed active knee range of motion and increased muscle strength, as well as a recovery of sensation. A positive linear correlation was found between MESS and the time required to achieve a reduction in swelling, as well as the time required for the recovery of sensation and knee range of motion (r>0.8; P<.05). Satisfactory clinical outcomes were obtained in patients with compartment syndrome of the thigh associated with acute renal failure.Urine alkalization, electrolyte and water balance, and continuous renal replacement therapy have played an important role in saving lives and extremities. Nonoperative treatment should be considered in the treatment of compartment syndrome of the thigh associated with acute renal failure. PMID:22495847

  15. Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice.

    PubMed

    Hosseinzadeh, H; Moallem, S A; Moshiri, M; Sarnavazi, M S; Etemad, L

    2012-07-01

    In this study, the anti-nociceptive and anti-inflammatory effects of cyanocobalamin (Vit B12) against acute and chronic pain and inflammation were evaluated in mice. Vit B12 (0.87, 1 and 1.77 mg/kg) were injected intraperitoneally. The anti-nociceptive effects against acute pain were examined using hot-plate and writhing tests. The chronic pain was examined 14 days after sciatic nerve ligation using the hot-plate test. Morphine (10 mg/kg) was used as a positive control. Anti-inflammatory effects of Vit B12 against acute and chronic inflammation were assessed using xylene-induced edema in ears and granuloma caused by compressed cotton implantation, respectively. In these tests, sodium diclofenac (15 mg/kg) was used as a positive control. Vit B12 showed a dose related effect in acute anti-nociceptive test and increased the anti-nociceptive effect of morphine in chronic treatment. Vit B12 demonstrated an anti-nociceptive effect in chronic studies as single or continues daily treatment and increased significantly the anti-nociceptive effect of morphine. All doses of Vit B12 significantly decreased xylene-induced ear edema. Maximum anti-inflammatory effect (37.5%) was obtained at dose of 1 mg/kg. In chronic inflammation, Vit B12 significantly decreased granuloma formation in mice. In conclusion our work presents some experimental evidence supporting the administration of cyanocobalamin in controlling acute and chronic neuropathic pain. Cyanocobalamin may have anti-inflammatory effect. It may reduce tolerance to anti-nociceptive effect of morphine as well. PMID:22588629

  16. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  17. Psychosocial Acute Treatment in Early-Episode Schizophrenia Disorders

    ERIC Educational Resources Information Center

    Bola, John R.

    2006-01-01

    Objective: This article reviews evidence on the treatment of early episode schizophrenia spectrum disorders that contradicts, in some cases, the American Psychiatric Association's generic recommendation of antipsychotic medication treatment for at least a year. Method: Evidence on lack of diagnostic validity, absence of demonstrated long-term…

  18. Endovascular treatment of nonvariceal acute arterial upper gastrointestinal bleeding

    PubMed Central

    Andersen, Poul Erik; Duvnjak, Stevo

    2010-01-01

    Transcatheter arterial embolization as treatment of upper nonvariceal gastrointestinal bleeding is increasingly being used after failed primary endoscopic treatment. The results after embolization have become better and surgery still has a high mortality. Embolization is a safe and effective procedure, but its use is has been limited because of relatively high rates of rebleeding and high mortality, both of which are associated with gastrointestinal bleeding and non-gastrointestinal related mortality causes. Transcatheter arterial embolization is a valuable minimal invasive method in the treatment of early rebleeding and does not involve a high risk of treatment associated complications. A multidisciplinary approach is necessary in the treatment of these patients and should comprise gastroenterologists, interventional radiologists, anaesthesiologists, and surgeons to achieve the best possible results. PMID:21160665

  19. The effect of chronic morphine or methadone exposure and withdrawal on clock gene expression in the rat suprachiasmatic nucleus and AA-NAT activity in the pineal gland.

    PubMed

    Pačesová, D; Novotný, J; Bendová, Z

    2016-07-18

    The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate addiction and drug withdrawal may affect circadian rhythmicity of various hormones or the sleep/activity pattern of many experimental subjects; however, limited research has been done on the long-term effects of sustained opiate administration on the intrinsic rhythmicity in the suprachiasmatic nucleus and pineal gland. Here we compared the effects of repeated daily treatment of rats with morphine or methadone and subsequent naloxone-precipitated withdrawal on the expression of the Per1, Per2, and Avp mRNAs in the suprachiasmatic nucleus and on arylalkylamine N-acetyltransferase activity in the pineal gland. We revealed that 10-day administration and withdrawal of both these drugs failed to affect clock genes and Avp expression in the SCN. Our results indicate that opioid-induced changes in behavioral and physiological rhythms originate in brain structures downstream of the suprachiasmatic nucleus regulatory output pathway. Furthermore, we observed that acute withdrawal from methadone markedly extended the period of high night AA-NAT activity in the pineal gland. This suggests that withdrawal from methadone, a widely used drug for the treatment of opioid dependence, may have stronger impact on melatonin synthesis than withdrawal from morphine. PMID:27070740

  20. Results of treatment with an intensive combination induction regimen containing idarubicin in children with acute myeloblastic leukemia: preliminary report of the Argentine Group for Treatment of Acute Leukemia.

    PubMed

    Sackmann-Muriel, F; Fernández-Barbieri, M A; Santarelli, M T; Matus-Ridley, M; Rosso, A; Negri-Aranguren, P; Cerutti, I; Gomel, M; Kvicala, R

    1993-12-01

    In April 1990, the Argentine Group for Treatment of Acute Leukemia began a multicenter trial for the treatment of previously untreated acute myeloblastic leukemia patients who were under 21 years of age. Initial treatment consisted of an 8-day induction phase with cytarabine together with idarubicin on days 3 to 5 and etoposide on days 6 to 8. A multidrug consolidation phase was subsequently administered and, after a treatment-free interval of 2 to 4 weeks, two 5-day intensification courses with high-dose cytarabine and etoposide were delivered with a 4-week interval between each course. Continuation therapy was started 2 to 4 weeks after the second course, with 6-thioguanine daily and cytarabine daily for 4 days every 4 weeks. Treatment was stopped after 18 months in children in continuous complete remission. A preliminary evaluation of this ongoing study included 36 patients with a mean age of 7.5 years (age range, 5 months to 16 years). The majority of patients had a French-American-British classification of M2 (n = 13) or M4 (n = 8). Complete remission was achieved by 91.7% of patients, while one died from sepsis in bone marrow hypoplasia and two were regarded as treatment failures. At a median follow-up of 12 months (range, 2 to 23 months) there were 12 adverse events: six bone marrow relapses, one bone marrow/skin relapse, and five deaths in complete remission (all deaths occurred during the consolidation phase). During the induction phase most of the patients experienced prolonged myelosuppression, and grade 3 to 4 toxicity (according to the Children's Cancer Group criteria) was frequently seen. Alopecia was universal. However, toxicity was manageable. We conclude that idarubicin in combination with cytarabine and etoposide is a highly effective regimen for induction in children with acute myeloblastic leukemia. PMID:8290970

  1. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    PubMed Central

    Jacob, Joe Antony; Salmani, Jumah Masoud Mohammad; Chen, Baoan

    2016-01-01

    Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration. This review focuses on the drugs under preclinical and clinical study in the ongoing efforts for treatment of acute and chronic lymphoblastic leukemia. PMID:27382259

  2. Synthesis of a novel photopolymerized nanocomposite hydrogel for the treatment of acute mechanical damage to cartilage

    NASA Astrophysics Data System (ADS)

    Schlichting, Kathryn; Copeland-Johnson, Trishelle; Goodman, Matthew; Lipert, Robert; McKinley, Todd; Martin, James; Mallapragada, Surya; Lin, Zhiqun

    2011-03-01

    Posttraumatic osteoarthritis is caused by a cascade of pathobiologic and pathomechanical events starting with intraarticular fractures in the cartilage. Currently, treatment of fractures is completely focused on restoration of the macroanatomy of the joint. The premise is that restoring the macroanatomy will prevent ongoing stresses and in turn prevent cartilage degeneration. However, current treatment ignores acute mechanical damage sustained by cartilage at the time of injury. This study describes the initial development of a novel nanocomposite photopolymerizing copolymer that has potential to restore local structural integrity to acutely injured cartilage, and subsequently act as a carrier for chondrocyte-enhancing bioactive agents.

  3. Morphine and microRNA Activity: Is There a Relation with Addiction?

    PubMed Central

    Rodríguez, Raquel E.

    2012-01-01

    When we talk about drug addiction, we are really dealing with an extremely complex system in which there still remain many unknowns and where many empty spaces or missing links are still present. Recent studies have identified changes in the expression profiles of several specific miRNAs which affect the interactions between these molecules and their targets in various illnesses, including addiction, and which may serve as valuable targets for more efficient therapies. In this review, we summarize results which clearly demonstrate that several morphine-related miRNAs have roles in the mechanisms that define addiction. In this regard, morphine has been shown to have an important role in the regulation of different miRNAs, such as miR-let-7 [which works as a mediator of the movement of the mu opioid receptor (MOR) mRNA into P-bodies, leading to translational repression], miR-23b (involved in linking MOR expression and morphine treatment at the post-transcriptional level), and miR-190 (a key post-transcriptional repressor of neurogenic differentiation, NeuroD). Fentanyl increases NeuroD levels by reducing the amount of miR-190, but morphine does not affect the levels of NeuroD. We also discuss the relationship between morphine, miRNAs, and the immune system, based on the discovery that morphine treatment of monocytes led to a decrease in several anti-HIV miRNAs (mir-28, 125b, 150, and 382). This review is centered on miR-133b and its possible involvement in addiction through the effects of morphine. We establish the importance of miR-133b as a regulatory factor by summarizing its activity in different pathological processes, especially cancer. Using the zebrafish as a research model, we discuss the relationship between mir-133b, the dopaminergic system, and morphine, considering: (1) that morphine modulates the expression of miR-133b and of its target transcript Pitx3, (2) the role of the zebrafish mu opioid receptor (zfMOR) in morphine-induced regulation of miR-133b

  4. A new approach to treatment of acute heart failure.

    PubMed

    Goldsmith, Steven R

    2016-05-01

    Conventional therapies for acute decongestion have yielded uniformly poor results in patients with acute heart failure (AHF). The failure of current strategies may be due to advanced disease in hospitalized patients, incomplete therapy, inherent limitations to existing therapy, or some combination of all three factors. Loop diuretics are the mainstay of current therapy and are in theory not ideal since while producing immediate intravascular volume reduction and relief of symptoms they activate neurohormonal forces that are deleterious to both the heart and the kidney. Ultrafiltration is an alternative to loop diuretics but has not proved advantageous in the setting of renal dysfunction, and if not carefully applied may also aggravate neurohormonal imbalance. In theory decongestive therapy for AHF should remove large volumes of fluid quickly and safely and improve symptoms, particularly dyspnea, without aggravating renal dysfunction or causing neurohormonal activation. Several studies have now suggested that the use of aquaretics such as antagonists to the V2 receptor for arginine vasopressin may be useful as adjunctive therapy in AHF, particularly when renal dysfunction and/or hyponatremia are present. These agents leverage osmotic forces to produce tissue decongestion while causing a water diuresis. They do not adversely affect renal function or neurohormonal balance. Building on the current base of knowledge about outcomes in AHF together with the only study of vasopressin antagonists as short-term monotherapy in chronic heart failure, it would be reasonable to design a trial in AHF in which the use of loop diuretics was minimized in favor of these agents. PMID:26946929

  5. Treatment advances have not improved the early death rate in acute promyelocytic leukemia

    PubMed Central

    McClellan, James Scott; Kohrt, Holbrook E.; Coutre, Steven; Gotlib, Jason R.; Majeti, Ravindra; Alizadeh, Ash A.; Medeiros, Bruno C.

    2012-01-01

    Early mortality in acute promyelocytic leukemia has been reported to occur in less than 10% of patients treated in clinical trials. This study reports the incidence and clinical features of acute promyelocytic leukemia patients treated at Stanford Hospital, CA, USA since March 1997, focusing on early mortality. We show that the risk of early death in acute promyelocytic leukemia patients is higher than previously reported. In a cohort of 70 patients who received induction therapy at Stanford Hospital, 19% and 26% died within seven and 30 days of admission, respectively. High early mortality was not limited to our institution as evaluation of the Surveillance, Epidemiology and End Results Database demonstrated that 30-day mortality for acute promyelocytic leukemia averaged 20% from 1977–2007 and did not improve significantly over this interval. Our findings show that early death is now the greatest contributor to treatment failure in this otherwise highly curable form of leukemia. PMID:21993679

  6. Morphine

    MedlinePlus

    ... breathing problems or other serious, life-threatening side effects. Tell your doctor if you are taking or plan to take any of the following medications: cimetidine (Tagamet); other narcotic pain medications; medications for anxiety, seizures, depression, mental illness, or nausea; muscle relaxants; ...

  7. Early treatment of acute migraine: new evidence of benefits.

    PubMed

    Valade, D

    2009-12-01

    The current management approach to migraine headaches advocates use of triptan medications early in the course of an attack while pain is still mild, rather than waiting to treat the pain when it has progressed to moderate-severe. Recently, strong new evidence for the benefits of early intervention has become available. The AEGIS, AIMS and AwM studies of almotriptan in patients with migraine indicate that earlier treatment initiation and lower pain intensity at the time of treatment are important predictors of enhanced therapeutic outcomes. The opportunity to treat early exists for about 50% of all migraine attacks, which offers considerable scope for improving migraine management. Importantly, treating pain early and before it has progressed beyond 'mild' meets many of the expectations patients have of their migraine treatment. It is believed that consistent, positive outcomes may assist in overcoming the various physician- and patient-perceived barriers to adoption of this beneficial treatment strategy. PMID:20017750

  8. Magnetic resonance diffusion tensor imaging following major ozonated autohemotherapy for treatment of acute cerebral infarction

    PubMed Central

    Wu, Xiao-na; Zhang, Tao; Wang, Jun; Liu, Xiao-yan; Li, Zhen-sheng; Xiang, Wei; Du, Wei-qing; Yang, Hong-jun; Xiong, Tie-gen; Deng, Wen-ting; Peng, Kai-run; Pan, Su-yue

    2016-01-01

    Major ozonated autohemotherapy has been shown to promote recovery of upper limb motor function in patients with acute cerebral infarction, but whether major ozonated autohemotherapy affects remote injury remains poorly understood. Here, we assumed that major ozonated autohemotherapy contributes to recovery of clinical function, possibly by reducing remote injury after acute cerebral infarction. Sixty acute cerebral infarction patients aged 30–80 years were equally and randomly allocated to ozone treatment and control groups. Patients in the ozone treatment group received medical treatment and major ozonated autohemotherapy (47 mg/L, 100 mL ozone) for 10 ± 2 days. Patients in the control group received medical treatment only. National Institutes of Health Stroke Scale score, modified Rankin scale score, and reduced degree of fractional anisotropy values of brain magnetic resonance diffusion tensor imaging were remarkably decreased, brain function improved, clinical efficiency significantly increased, and no obvious adverse reactions detected in the ozone treatment group compared with the control group. These findings suggest that major ozonated autohemotherapy promotes recovery of neurological function in acute cerebral infarction patients by reducing remote injury, and additionally, exhibits high safety.

  9. Ecallantide: a plasma kallikrein inhibitor for the treatment of acute attacks of hereditary angioedema.

    PubMed

    Stolz, L E; Horn, P T

    2010-08-01

    Hereditary angioedema (HAE) is a debilitating, potentially fatal disease characterized by variable and unpredictable acute attacks of swelling affecting the subcutaneous tissue and mucosa. It is an autosomal dominant disorder resulting from a genetic deficiency of functional C1-esterase inhibitor. Available treatments include long-term prophylaxis, short-term prophylaxis and treatment of acute attacks. Ecallantide is a novel, specific and potent inhibitor of plasma kallikrein that was recently approved in the United States for the treatment of acute attacks of HAE in patients aged 16 years and older. In two phase III clinical trials, the subcutaneous administration of 30 mg ecallantide resulted in significantly greater symptom improvement than placebo for acute attacks of HAE. Ecallantide was generally well tolerated throughout the clinical development program. The main safety concern following ecallantide treatment is hypersensitivity reactions, including anaphylaxis. A Risk Evaluation and Management Strategy (REMS) has been implemented to minimize this risk and a long-term observational safety study is currently under way to collect more information about hypersensitivity and immunogenicity. Ecallantide represents a novel treatment option for patients with HAE. PMID:20830315

  10. Arthroscopically Assisted Treatment of Acute Dislocations of the Acromioclavicular Joint

    PubMed Central

    Braun, Sepp; Beitzel, Knut; Buchmann, Stefan; Imhoff, Andreas B.

    2015-01-01

    Arthroscopically assisted treatments for dislocations of the acromioclavicular joint combine the advantages of exact and visually controlled coracoid tunnel placement with the possibility of simultaneous treatment of concomitant injuries. The clinical results of previous arthroscopically assisted techniques have been favorable at midterm and long-term follow-up. The presented surgical technique combines the advantages of arthroscopically positioned coracoclavicular stabilization with an additional suture cord cerclage of the acromioclavicular joint capsule for improved horizontal stability. PMID:26870646

  11. Acute severe asthma: new approaches to assessment and treatment.

    PubMed

    Papiris, Spyros A; Manali, Effrosyni D; Kolilekas, Likurgos; Triantafillidou, Christina; Tsangaris, Iraklis

    2009-01-01

    The precise definition of a severe asthmatic exacerbation is an issue that presents difficulties. The term 'status asthmaticus' relates severity to outcome and has been used to define a severe asthmatic exacerbation that does not respond to and/or perilously delays the repetitive or continuous administration of short-acting inhaled beta(2)-adrenergic receptor agonists (SABA) in the emergency setting. However, a number of limitations exist concerning the quantification of unresponsiveness. Therefore, the term 'acute severe asthma' is widely used, relating severity mostly to a combination of the presenting signs and symptoms and the severity of the cardiorespiratory abnormalities observed, although it is well known that presentation does not foretell outcome. In an acute severe asthma episode, close observation plus aggressive administration of bronchodilators (SABAs plus ipratropium bromide via a nebulizer driven by oxygen) and oral or intravenous corticosteroids are necessary to arrest the progression to severe hypercapnic respiratory failure leading to a decrease in consciousness that requires intensive care unit (ICU) admission and, eventually, ventilatory support. Adjunctive therapies (intravenous magnesium sulfate and/or others) should be considered in order to avoid intubation. Management after admission to the hospital ward because of an incomplete response is similar. The decision to intubate is essentially based on clinical judgement. Although cardiac or respiratory arrest represents an absolute indication for intubation, the usual picture is that of a conscious patient struggling to breathe. Factors associated with the increased likelihood of intubation include exhaustion and fatigue despite maximal therapy, deteriorating mental status, refractory hypoxaemia, increasing hypercapnia, haemodynamic instability and impending coma or apnoea. To intubate, sedation is indicated in order to improve comfort, safety and patient-ventilator synchrony, while at the

  12. The role of morphine in a rat model of hypoxic-ischemic injury.

    PubMed

    Festekjian, Ara; Ashwal, Stephen; Obenaus, Andre; Angeles, Danilyn M; Denmark, T Kent

    2011-08-01

    We investigated whether morphine plays a neuroprotective role in a neonatal rat pup model of bilateral carotid artery occlusion with hypoxia. At postnatal day 10, rats received either morphine (n = 7), naloxone (n = 7), or saline placebo (n = 15) after hypoxic-ischemic injury. Survival (days), weight gain and animal testing (negative geotaxis, surface righting, and rotarod) were compared between treatment groups. Lesion volume was delineated with magnetic resonance imaging at days 7 and 28-57 after injury. Survival in rats treated with morphine, naloxone, or saline was, respectively, 14, 29, and 73%. Median number of days of survival after bilateral carotid artery occlusion with hypoxia treated with morphine was 4 (95% confidence interval 4 to 22), with naloxone was 3 (95% confidence interval -1.4 to 21), and with placebo was 28 (95% confidence interval 18 to 28). There were no statistically significant differences in magnetic resonance imaging-derived ischemic lesion volumes, weight gain, or behavioral testing measures between the groups. Morphine was ineffective as a neuroprotectant in rat pups with severe hypoxic-ischemic injury and may have contributed to their decreased survival. PMID:21763946

  13. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice.

    PubMed

    Kim, Woojin; Kim, Min Joon; Go, Donghyun; Min, Byung-Il; Na, Heung Sik; Kim, Sun Kwang

    2016-02-01

    Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg) or 5-HT3 (MDL-72222, 15 μg) receptor antagonist, but not with α2 adrenergic (idazoxan, 10 μg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain. PMID:26805884

  14. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice

    PubMed Central

    Kim, Woojin; Kim, Min Joon; Go, Donghyun; Min, Byung-Il; Na, Heung Sik; Kim, Sun Kwang

    2016-01-01

    Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg) or 5-HT3 (MDL-72222, 15 μg) receptor antagonist, but not with α2-adrenergic (idazoxan, 10 μg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain. PMID:26805884

  15. L-type calcium channel blockers, morphine and pain: Newer insights

    PubMed Central

    Kumar, Rakesh; Mehra, RD; Ray, S Basu

    2010-01-01

    Earlier, we had reported that co-administration of opioids and L-type calcium channel blockers (L-CCBs) like diltiazem could prove useful in the treatment of cancer pain. Much of this report was based upon earlier published work involving animal models of pain exposed to brief periods of noxious radiant heat without any tissue injury. However, pain in clinical situations usually result from tissue injury. Thus, the aim of the current investigation was to study the analgesic effect of this combination of drugs in the rat formalin test which is associated with actual tissue injury. Wistar rats (n=60) received either L-CCB (nifedipine/nimodipine/verapamil/diltiazem i.p.) or morphine (s.c.) or both drugs. The formalin test was done 30 min after morphine or placebo injection. The naloxone reversal test was also done. Administration of L-CCBs alone, particularly diltiazem, increased pain in the formalin test. In contrast, co-administration of these L-CCBs with morphine led to decreased pain response, though statistically significant decrease was noted only with nimodipine + morphine. Naloxone reversed this analgesic effect, indicating that it was primarily an opioid-mediated effect. The results show that administration of L-CCBs alone may prove counterproductive in the therapeutic management of pain (anti-analgesic effect). However, co-administration of both drugs (morphine and nimodipine) in quick succession could lead to adequate pain relief. PMID:20661350

  16. Can personality traits and gender predict the response to morphine? An experimental cold pain study.

    PubMed

    Pud, Dorit; Yarnitsky, David; Sprecher, Elliot; Rogowski, Zeev; Adler, Rivka; Eisenberg, Elon

    2006-02-01

    The aim of the present study was to examine the possible role of personality traits, in accordance with Cloninger's theory, and gender, in the variability of responsiveness to opioids. Specifically, it was intended to test whether or not the three personality dimensions - harm avoidance (HA), reward dependence (RD) and novelty seeking (NS) - as suggested by Cloninger, can predict inter-personal differences in responsiveness to morphine after exposure to experimental cold pain. Thirty-four healthy volunteers (15 females, 19 males) were given the cold pressor test (CPT). Pain threshold, tolerance, and magnitude (VAS) were measured before and after (six measures, 30 min apart) the administration of either 0.5 mg/kg oral morphine sulphate (n=21) or 0.33 mg/kg oral active placebo (diphenhydramine) (n=13) in a randomized, double blind design. Assessment of the three personality traits, according to Cloninger's Tridimensional Personality Questionnaire, was performed before the CPT. A high HA score (but not RD, NS, or baseline values of the three pain parameters) predicted a significantly larger pain relief following the administration of morphine sulphate (but not of the placebo). Women exhibited a larger response in response to both treatments, as indicated by a significantly increased threshold and tolerance following morphine sulphate as well as significantly increased tolerance and decreased magnitude following placebo administration. The present study confirms the existence of individual differences in response to analgesic treatment. It suggests that high HA personality trait is associated with better responsiveness to morphine treatment, and that females respond better than men to both morphine and placebo. PMID:16310713

  17. [Current approaches to the treatment of severe hypoxic respiratory insufficiency (acute lung injury; acute respiratory distress syndrome)].

    PubMed

    Kluge, S; Müller, T; Pfeifer, M

    2011-02-01

    Lung-protective ventilation with a low tidal volume, plateau pressure < 30 cm H(2)O. oxygen saturation > 90% and permissive hypercapnia results in reduction of the mortality rate in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The level of the positive end-expiratory pressure (PEEP) must be chosen in relation to oxygen requirement. High frequency oscillatory ventilation and neurally adjusted ventilatory assist are promising methods. However, further studies with firm end-points have to be awaited before a final judgment is possible. Veno-venous extracorporeal membrane oxygenation (ECMO) can ensure life-sustaining gas exchange in patients with severe vitally compromised pulmonary failure, to provide time for lung tissue to heal and reduce ventilatory stress. The latest guidelines for analgesia and sedation in intensive care medicine demand consistent monitoring of the level of sedation and the intensity of pain. The sedation should be interrupted daily, with phases of awakenings and, if possible, spontaneous breathing. Methods of supportive treatment: Positional treatment (prone position) and inhalation of vasodilators can improve ventilation/perfusion mismatch and thus oxygenation. However, administration of surfactant is currently not advised in adult respiratory failure. PMID:21271478

  18. Recent advances in the treatment of colonic diverticular disease and prevention of acute diverticulitis.

    PubMed

    Elisei, Walter; Tursi, Antonio

    2016-01-01

    The incidence of diverticulosis and diverticular disease of the colon is increasing worldwide. Although the majority of patients remains asymptomatic long-life, the prevalence of diverticular disease of the colon, including acute diverticulitis, is substantial and is becoming a significant burden on National Health Systems in terms of direct and indirect costs. Focus is now being drawn on identifying the correct therapeutic approach by testing various treatments. Fiber, non-absorbable antibiotics and probiotics seem to be effective in treating symptomatic and uncomplicated patients, and 5-aminosalicylic acid might help prevent acute diverticulitis. Unfortunately, robust evidence on the effectiveness of a medical strategy to prevent acute diverticulitis recurrence is still lacking. We herein provide a concise review on the effectiveness and future perspectives of these treatments. PMID:26752946

  19. Recent advances in the treatment of colonic diverticular disease and prevention of acute diverticulitis

    PubMed Central

    Elisei, Walter; Tursi, Antonio

    2016-01-01

    The incidence of diverticulosis and diverticular disease of the colon is increasing worldwide. Although the majority of patients remains asymptomatic long-life, the prevalence of diverticular disease of the colon, including acute diverticulitis, is substantial and is becoming a significant burden on National Health Systems in terms of direct and indirect costs. Focus is now being drawn on identifying the correct therapeutic approach by testing various treatments. Fiber, non-absorbable antibiotics and probiotics seem to be effective in treating symptomatic and uncomplicated patients, and 5-aminosalicylic acid might help prevent acute diverticulitis. Unfortunately, robust evidence on the effectiveness of a medical strategy to prevent acute diverticulitis recurrence is still lacking. We herein provide a concise review on the effectiveness and future perspectives of these treatments. PMID:26752946

  20. Current standard treatment of adult acute promyelocytic leukaemia.

    PubMed

    Lo-Coco, Francesco; Cicconi, Laura; Breccia, Massimo

    2016-03-01

    The outcome of patients with acute promyelocytic leukaemia (APL) has dramatically improved over the last two decades, due to the introduction of combined all-trans retinoic acid (ATRA) and chemotherapy regimens and, more recently, to the advent of arsenic trioxide (ATO). ATRA and anthracycline-based chemotherapy remains a widely used strategy, providing cure rates above 80%, but it is associated with risk of severe infections and occurrence of secondary leukaemias. ATO is the most effective single agent in APL and, used alone or in combination with ATRA or ATRA and reduced-intensity chemotherapy, results in greater efficacy with considerably less haematological toxicity. The toxic profile of ATO includes frequent, but manageable, QTc prolongation and increase of liver enzymes. Two large randomized studies have shown that ATRA + ATO is superior to ATRA + chemotherapy for newly diagnosed low-risk APL resulting in 2-4 year event-free survival rates above 90% and very few relapses. According to real world data, the spectacular progress in APL outcomes reported in clinical trials has not been paralleled by a significant improvement in early death rates, this remains the most challenging issue for the final cure of the disease. PMID:26687281

  1. Treatment of severe acute pancreatitis and its complications.

    PubMed

    Zerem, Enver

    2014-10-14

    Severe acute pancreatitis (SAP), which is the most serious type of this disorder, is associated with high morbidity and mortality. SAP runs a biphasic course. During the first 1-2 wk, a pro-inflammatory response results in systemic inflammatory response syndrome (SIRS). If the SIRS is severe, it can lead to early multisystem organ failure (MOF). After the first 1-2 wk, a transition from a pro-inflammatory response to an anti-inflammatory response occurs; during this transition, the patient is at risk for intestinal flora translocation and the development of secondary infection of the necrotic tissue, which can result in sepsis and late MOF. Many recommendations have been made regarding SAP management and its complications. However, despite the reduction in overall mortality in the last decade, SAP is still associated with high mortality. In the majority of cases, sterile necrosis should be managed conservatively, whereas in infected necrotizing pancreatitis, the infected non-vital solid tissue should be removed to control the sepsis. Intervention should be delayed for as long as possible to allow better demarcation and liquefaction of the necrosis. Currently, the step-up approach (delay, drain, and debride) may be considered as the reference standard intervention for this disorder. PMID:25320523

  2. Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference.

    PubMed

    Gramage, Esther; Vicente-Rodríguez, Marta; Herradón, Gonzalo

    2015-09-14

    Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction and neurodegenerative disorders. Morphine administration induces an increase in the expression of PTN and Midkine (MK), the only other member of this family of cytokines, in brain areas related with the addictive effects of drug of abuse, like the Ventral Tegmental Area or the hippocampus. In spite of previous studies showing that PTN modulates amphetamine and ethanol rewarding effects, and that PTN is involved in morphine-induced analgesia, it was still unknown if the rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to study the role of PTN in the reward and physical dependence induced by morphine. We used the Conditioned Place Preference (CPP) paradigm in PTN genetically deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of morphine in absence of endogenous PTN. Second, to study if PTN may be involved in morphine physical dependence, naloxone-precipitated withdrawal syndrome was induced in PTN-/- and WT morphine dependent mice. Although the increase in the time spent in the morphine-paired compartment after conditioning tended to be more pronounced in PTN-/- mice, statistical significance was not achieved. The data suggest that PTN does not exert an important role in morphine reward. However, our results clearly indicate that PTN-/- mice develop a more severe withdrawal syndrome than WT mice, characterized as a significant increase in the time standing and in the total incidences of forepaw licking, forepaw tremors, wet dog shake and writhing. The data presented here suggest that PTN is a novel genetic factor that plays a role in morphine withdrawal syndrome. PMID:26222257

  3. ¹H NMR-based metabonomic analysis of brain in rats of morphine dependence and withdrawal intervention.

    PubMed

    Hu, Zhengtao; Deng, Yi; Hu, Chunyan; Deng, Pengchi; Bu, Qian; Yan, Guangyan; Zhou, Jiaqing; Shao, Xue; Zhao, Jinxuan; Li, Yan; Zhu, Ruiming; Xu, Youzhi; Zhao, Yinglan; Cen, Xiaobo

    2012-05-16

    Metabolic consequences of morphine dependence and withdrawal intervention have not been well explored. In the present study, the metabolic changes in brain hippocampus, nucleus accumbens (NAc), prefrontal cortex (PFC) and striatum of rats with morphine dependence and withdrawal intervention were explored by using ¹H nuclear magnetic resonance coupled with principal component analysis, partial least squares and orthogonal signal correction analysis. We found that the concentrations of neurotransmitters including glutamate, glutamine and gamma-aminobutyric acid changed differentially in hippocampus, NAc, PFC and striatum after repeated morphine treatment. Significant changes were also found in a number of cerebral metabolites including N-acetyl aspartate (NAA), lactic acid, creatine, myo-inositol and taurine. These findings indicate the profound disturbances of energy metabolism, amino acid metabolism and neurotransmitters caused by chronic morphine treatment. Interestingly, morphine-induced changes in lactic acid, creatine and NAA were clearly reversed by intervention of methadone or clonidine. Our study provides a comprehensive understanding of the metabolic alteration associated with morphine addiction and withdrawal therapy, which may help to develop new pharmacotherapies. PMID:22391120

  4. Treatment of Acute Puerperal Mastitis and Breast Abscess

    PubMed Central

    Cantlie, Helene Bertrand

    1988-01-01

    Mastitis is a benign infection of the breast if it is treated early. If two days elapse before treatment is started, it can lead to serious complications such as chronic or recurrent mastitis or breast abscess. Treatment consists in frequent nursing and massaging or stripping the breast to keep it empty of milk or pus, and appropriate antibiotics. Incision and drainage of a breast abscess can be done in the office under local anesthesia, and the drainage continued at home by the mother. PMID:21253250

  5. Acute bilateral glaucoma and panuveitis as a side effect of topiramate for weight loss treatment.

    PubMed

    Pikkel, Yoav Yechezkel

    2014-01-01

    A 54-year-old male patient presented to our clinic with acute angle-closure glaucoma and panuveitis in both eyes after being treated with topiramate for binge eating and obesity. This case report emphasises the hazardous side effects of treatment with topiramate with unusual indication and the precaution a caretaker must take when treating a patient. PMID:24744070

  6. Effective treatment of migraine. Terminating acute attacks, reducing their frequency.

    PubMed

    Pringsheim, Tamara; Edmeads, John

    2004-04-01

    Migraine is the headache most commonly encountered in primary care practice. In one US population survey, 17.6% of women and 6% of men reported migraine. Specific, effective treatment options for migraine are increasingly available, helping to reinforce how important it is that this common and sometimes disabling condition be recognized by primary care physicians. PMID:15095534

  7. The Influence of Genotype Polymorphism on Morphine Analgesic Effect for Postoperative Pain in Children

    PubMed Central

    Lee, Mi Geum; Kim, Hyun Jung; Lee, Keun Hwa

    2016-01-01

    Background Although opioids are the most commonly used medications to control postoperative pain in children, the analgesic effects could have a large inter-individual variability according to genotypes. The aim of this study was to investigate the association between single nucleotide polymorphisms and the analgesic effect of morphine for postoperative pain in children. Methods A prospective study was conducted in 88 healthy children undergoing tonsillectomy, who received morphine during the operation. The postoperative pain score, frequency of rescue analgesics, and side effects of morphine were assessed in the post-anesthesia care unit. The children were genotyped for OPRM1 A118G, ABCB1 C3435T, and COMT Val158Met. Results Children with at least one G allele for OPRM1 (AG/GG) had higher postoperative pain scores compared with those with the AA genotype at the time of discharge from the post-anesthesia care unit (P = 0.025). Other recovery profiles were not significantly different between the two groups. There was no significant relationship between genotypes and postoperative pain scores in analysis of ABCB1 and COMT polymorphisms. Conclusions Genetic polymorphism at OPRM1 A118G, but not at ABCB1 C3435T and COMT Val158Met, influences the analgesic effect of morphine for immediate acute postoperative pain in children. PMID:26839669

  8. [Treatment of acute pelvic inflammatory diseases with a new antibiotic compound preparation (author's transl)].

    PubMed

    Burmucic, R

    1980-11-30

    48 patients with acute pelvic inflammatory diseases (35 cases of acute adnexitis and 13 cases of inflammatory adnexal tumours) were treated with an antibiotic combination of Ampicillin/Oxacillin and Sisomicin. As initial parenteral therapy Ampicillin/Oxacillin 3.0 g was given intravenously twice daily and additionally Sisomicin 75 or 100 mg according to the body-weight was administered intramuscular twice daily. If required a further oral treatment with 500 mg Ampicillin/Dicloxacillin capsules four times a day was carried out. The average duration of parenteral treatment was 6.3 days; together with the oral treatment the duration of antibiotic treatment was 18.5 days. In 43 patients (89.6%) the disease could be cured completely or a distinct improvement could be achieved. Only in 5 cases (10.4%) the results were unsatisfactory. As side-effects allergic reactions were observed in three cases and gastro-enteritis in one case. PMID:7467388

  9. Ibuprofen in the treatment of acute ankle joint injuries. A double-blind study.

    PubMed

    Fredberg, U; Hansen, P A; Skinhøj, A

    1989-01-01

    Sixty-eight patients who presented to the casualty ward with acute ankle joint injuries were studied to examine the effect of ibuprofen on pain and ankle swelling. Thirty-two patients were treated with placebo tablets and 36 with 600 mg ibuprofen tablets taken four times a day for 4 to 6 days. All of the patients were immobilized and requested to keep the foot elevated. The results showed that ibuprofen had no effect on the ankle swelling. The need for additional analgesics was not influenced by treatment with ibuprofen, which means that ibuprofen has no effect on pain. The time elapsed from occurrence of the injury to arrival at the casualty ward was negatively correlated to the reduction of ankle joint swelling during the treatment period. Treatment with ice-sprays, icebags, or cold water during the acute stage of injury did not influence the reduction of swelling during the treatment period. PMID:2675651

  10. Guidelines for the diagnosis and treatment of acute and subacute rhinosinusitis in children.

    PubMed

    Esposito, S; Principi, N

    2008-04-01

    The importance of rhinosinusitis finally reached pediatricians' attention a few years ago, and it has now been demonstrated that it is medically important and has a considerable socioeconomic impact in childhood. These guidelines, which have been prepared with and approved by many Italian Scientific Societies, are based on the most recent findings in the fields of clinical symptoms, imaging and microbiology tests for the diagnosis of acute rhinosinusitis, and efficacy evidence concerning antibiotic treatment and non-antibiotic adjuvant treatment. A Pubmed search using the key words "sinusitis", "rhinosinusitis", "child" and "antibiotic treatment", and the limits "human studies" and "English language", led to the selection of more than 2,700 articles published between 1966 and 2007. These guidelines are based on the 125 that were considered truly relevant and reflect the most widely shared positions concerning the diagnosis and treatment of acute, subacute and recurrent rhinosinusitis in children. PMID:18467238

  11. Stem cell technology for the treatment of acute and chronic renal failure

    PubMed Central

    Pino, Christopher J.; Humes, H. David

    2010-01-01

    Acute and chronic renal failure are disorders with high rates of morbidity and mortality. Current treatment is based upon conventional dialysis to provide volume regulation and small solute clearance. There is growing recognition that renal failure is a complex disease state requiring a multifactorial therapy to address the short-comings of the conventional monofactorial approach. Kidney transplantation remains the most effective treatment, however, organ availability lags far behind demand. Many key kidney functions including gluconeogenesis, ammoniagenesis, metabolism of glutathione, catabolism of important peptide hormones, growth factors, and cytokines critical to multiorgan homeostasis and immunomodulation are provided by renal tubule cells. Therefore, cell-based therapies are promising multifactorial treatment approaches. In this review, current stem cell technologies including adult stem cells, embryonic stem cells and induced pluripotent stem cells will be discussed as cell sources for the treatment of acute and chronic renal failure. PMID:20801413

  12. Effects of morphine on the disposition of ampicillin in mice.

    PubMed Central

    Garty, M; Hurwitz, A

    1985-01-01

    Morphine raised the levels of intravenously administered ampicillin in the plasma of mice. Despite higher ampicillin levels in plasma after administration of morphine, levels of this antibiotic in bile and urine were not elevated. After ligation of the common bile duct, ampicillin levels in plasma were elevated. Morphine caused a further rise in drug levels in plasma of duct-ligated mice. Ampicillin levels in plasma were higher in mice made anephric by prolonged ligation of their external urethras. In such animals, morphine also caused ampicillin levels in plasma to be even higher. These experiments suggest that morphine impairs both renal and hepatobiliary elimination of ampicillin. These effects of morphine were completely reversed by naloxone. In contrast to effects on intravenously administered ampicillin, morphine markedly reduced drug levels in plasma when ampicillin was given by gastric intubation. This resulted from delayed absorption because of retardation of gastric emptying by morphine. PMID:4073871

  13. Stigma as a barrier to treatment for child acute malnutrition in Marsabit County, Kenya.

    PubMed

    Bliss, Jessica Robin; Njenga, Martin; Stoltzfus, Rebecca Joyce; Pelletier, David Louis

    2016-01-01

    Acute malnutrition affects millions of children each year, yet global coverage of life-saving treatment through the community-based management of acute malnutrition (CMAM) is estimated to be below 15%. We investigated the potential role of stigma as a barrier to accessing CMAM. We surveyed caregivers bringing children to rural health facilities in Marsabit County, Kenya, divided into three strata based on the mid-upper arm circumference of the child: normal status (n = 327), moderate acute malnutrition (MAM, n = 241) and severe acute malnutrition (SAM, n = 143). We used multilevel mixed effects logistic regression to estimate the odds of reporting shame as a barrier to accessing health care. We found that the most common barriers to accessing child health care were those known to be universally problematic: women's time and labour constraints. These constituted the top five most frequently reported barriers regardless of child acute malnutrition status. In contrast, the odds of reporting shame as a barrier were 3.64 (confidence interval: 1.66-8.03, P < 0.05) times higher in caregivers of MAM and SAM children relative to those of normal children. We conclude that stigma is an under-recognized barrier to accessing CMAM and may constrain programme coverage. In light of the large gap in coverage of CMAM, there is an urgent need to understand the sources of acute malnutrition-associated stigma and adopt effective means of de-stigmatization. PMID:25989353

  14. Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

    Cancer.gov

    This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes. |

  15. Acute Thrombotic Mesenteric Ischemia: Primary Endovascular Treatment in Eight Patients

    SciTech Connect

    Gagniere, Johan; Favrolt, Gregory; Alfidja, Agaiecha; Kastler, Adrian; Chabrot, Pascal; Cassagnes, Lucie; Buc, Emmanuel; Pezet, Denis; Boyer, Louis

    2011-10-15

    Introduction: The purpose of this study was to evaluate our experience with initial percutaneous transluminal angioplasty (PTA) {+-} stenting as valuable options in the acute setting. Methods: Between 2003 and 2008, eight patients with abdominal angio-MDCT-scan proven thrombotic AMI benefited from initial PTA {+-} stenting. We retrospectively assessed clinical and radiological findings and their management. Seven patients presented thrombosis of the superior mesenteric artery, and in one patient both mesenteric arteries were occluded. All patients underwent initial PTA and stenting, except one who had balloon PTA alone. One patient was treated by additional in situ thrombolysis. Results: Technical success was obtained in all patients. Three patients required subsequent surgery (37.5%), two of whom had severe radiological findings (pneumatosis intestinalis and/or portal venous gas). Two patients (25%) died: both had NIDD, an ASA score {>=}4, and severe radiologic findings. Satisfactory arterial patency was observed after a follow-up of 15 (range, 11-17) months in five patients who did not require subsequent surgery, four of whom had abdominal guarding but no severe CT scan findings. One patient had an ileocecal stenosis 60 days after the procedure. Conclusions: Initial PTA {+-} stenting is a valuable alternative to surgery for patients with thrombotic AMI even for those with clinical peritoneal irritation signs and/or severe radiologic findings. Early surgery is indicated if clinical condition does not improve after PTA. The decision of a subsequent surgery must be lead by early clinical status reevaluation. In case of underlying atherosclerotic lesion, stenting should be performed after initial balloon dilatation.

  16. Dalbavancin for the treatment of acute bacterial skin and skin structure infections.

    PubMed

    Esposito, Silvano; Noviello, Silvana; Leone, Sebastiano

    2015-12-01

    Dalbavancin is a novel parenteral lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults. Dalbavancin is highly active against common Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin has a prolonged half-life that allows for once weekly dosing. Phase III trials have demonstrated non-inferiority compared with vancomycin/linezolid in the treatment of ABSSSIs, including those sustained by MRSA. PMID:26700080

  17. Paliperidone palmitate injection for the acute and maintenance treatment of schizophrenia in adults

    PubMed Central

    Kim, Shiyun; Solari, Hugo; Weiden, Peter J; Bishop, Jeffrey R

    2012-01-01

    Purpose To review the use of paliperidone palmitate in treatment of patients with schizophrenia. Methods Published clinical trial data for the development and utilization of paliperidone palmitate for the treatment of schizophrenia were assessed in this review. Four short-term, randomized, double-blind, placebo-controlled trials investigated the efficacy of paliperidone palmitate in acute exacerbation of schizophrenia. Paliperidone palmitate was also studied as a maintenance treatment to prevent or delay relapse in stable schizophrenia. In addition, paliperidone palmitate was compared to risperidone long-acting injection for noninferiority in three studies. Results Paliperidone palmitate has been shown to be effective in reducing symptoms as measured by the Positive and Negative Syndrome Scale total scores in the four acute treatment studies. In the maintenance treatment studies, paliperidone palmitate was found to be more effective than placebo in preventing or delaying the time to first relapse in stable schizophrenia patients. In addition, paliperidone palmitate was shown to be noninferior to risperidone long-acting injection in two studies. It was shown to be reasonably well tolerated in all clinical trials. Acute treatment phase should be initiated with a dose of 234 mg on day one and 156 mg on day eight, followed by a recommended monthly maintenance dose of 39–234 mg based on efficacy and tolerability results from the clinical studies. Conclusion Providing an optimal long-term treatment can be challenging. Paliperidone palmitate can be used as an acute treatment even in outpatient setting, and it has shown to be well tolerated by patients. Also, it does not require overlapping oral antipsychotic supplementation while being initiated, and is dosed once per month. PMID:22879739

  18. [Peppermint oil in the acute treatment of tension-type headache].

    PubMed

    Göbel, H; Heinze, A; Heinze-Kuhn, K; Göbel, A; Göbel, C

    2016-06-01

    Tension-type headache is the most frequent form of headache. The local topical treatment with peppermint oil (oleum menthae piperitae) has proven to be significantly more effective than placebo in controlled studies. Peppermint oil targets headache pathophysiology in multiple ways. The efficacy is comparable to that of acetylsalicylic acid or paracetamol. Solutions of 10 % peppermint oil in ethanol are licensed for the treatment of tension-type headache in adults and children above 6 years. It is included in treatment recommendations and guidelines by the respective professional societies and is regarded as a standard treatment for the acute therapy of tension-type headaches. PMID:27106030

  19. Advancements in the treatment of pediatric acute leukemia and brain tumor - continuous efforts for 100% cure.

    PubMed

    Ju, Hee Young; Hong, Che Ry; Shin, Hee Young

    2014-10-01

    Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered. PMID:25379043

  20. [Acute hemorrhagic necrosis of the breast following treatment with Cumarin].

    PubMed

    Lüchtrath, H; Walkowsky, A

    1983-08-01

    A case of hemorrhagic necrosis of the breast is reported in a thirty-four year old woman who received Cumarin treatment for deep leg vein thrombosis and pulmonary embolism. It was necessary to remove the breast. The microscopic examination showed complete blockage of the vessels by fibrin thrombi in almost all veins. The cause of this venous thrombosis was explained as a Shwartzman-Sanarelli-Phenomenon. PMID:6555120

  1. The bioavailability of morphine applied topically to cutaneous ulcers.

    PubMed

    Ribeiro, Maria D C; Joel, Simon P; Zeppetella, Giovambattista

    2004-05-01

    A number of studies have reported the analgesic effect of morphine when applied topically to painful skin ulcers. It has been suggested that morphine may exert a local action, as opioid receptors have been demonstrated on peripheral nerve terminals. In this study, we investigated the bioavailability of topically applied morphine to cutaneous ulcers. Six hospice inpatients with skin ulcers were given morphine sulfate 10 mg in Intrasite gel topically and morphine sulfate 10 mg subcutaneously over 4 hours, at least 48 hours apart, in randomized order. Morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) were determined in plasma using a specific HPLC method. In five patients morphine and its metabolites were undetectable when applied topically. In one patient (with the largest ulcer), morphine and M6G were detected. The calculated morphine and M6G bioavailability in this patient were 20% and 21%, respectively. M3G was also detected but was below the lower limit of quantitation. When applied topically to ulcers, morphine was not absorbed in the majority of patients, suggesting any analgesic effect would be mediated locally rather than systemically. However, in ulcers with a large surface area, systemic absorption may occur. PMID:15120772

  2. Evolving strategies in the treatment of acute myocardial infarction-induced cardiogenic shock

    PubMed Central

    Tchantchaleishvili, Vakhtang; Schubmehl, Heidi; Swartz, Michael F.; Hallinan, William

    2014-01-01

    Despite advances in medical technology and re-vascularization interventions, the mortality rate for cardiogenic shock (CS) following acute myocardial infarction has remained at 50%. The majority of these mortalities are from left ventricular failure resulting in multi-system organ dysfunction. The field of mechanical circulatory support (MCS) has evolved within the past decade, with improved outcomes from extracorporeal membrane oxygenation as well as continuous-flow left ventricular assist devices (CF LVADs). In this paper, we discuss our institutional treatment strategies, the rationale for the protocol development, and our improved outcomes when using MCS in patients with refractory CS following acute myocardial infarction. PMID:25512903

  3. Time Dependent Antinociceptive Effects of Morphine and Tramadol in the Hot Plate Test: Using Different Methods of Drug Administration in Female Rats

    PubMed Central

    Gholami, Morteza; Saboory, Ehsan; Mehraban, Sogol; Niakani, Afsaneh; Banihabib, Nafiseh; Azad, Mohamad-Reza; Fereidoni, Javid

    2015-01-01

    Morphine and tramadol which have analgesic effects can be administered acutely or chronically. This study tried to investigate the effect of these drugs at various times by using different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult female rats were divided into six groups. They received saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1st, 8th and 15th days. After drug withdrawal, the hot plate test was repeated at the 17th, 19th, and 22nd days. There was a significant correlation between the day, drug, group, and their interaction (P<0.001). At 1st day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing to the saline groups (P<0.001), while there was no correlation between drug administration methods of morphine and/or tramadol. At the 8th day (d8), morphine and tramadol led to the most powerful analgesic effect comparing to the other experimental days (P<0.001). At the 15th day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually decrease and reach to a level compatible to d1. The present data also indicated that although the analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to them may not lead to altered nociceptive responses later in life. PMID:25561936

  4. The effect of different durations of morphine exposure on mesencephalic dopaminergic neurons in morphine dependent rats.

    PubMed

    Shi, Weibo; Ma, Chunling; Qi, Qian; Liu, Lizhe; Bi, Haitao; Cong, Bin; Li, Yingmin

    2015-12-01

    Mesencephalic dopaminergic neurons are heavily involved in the development of drug dependence. Thyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, plays an important role in the survival of dopaminergic neurons. Therefore, this study investigated TH changes in dopaminergic neurons of the ventral tegmental area (VTA) and substantia nigra (SN), as well as the morphine effects on dopaminergic neurons induced by different durations of morphine dependence. Models of morphine dependence were established in rats, and paraffin-embedded sections, immunohistochemistry and western blotting were used to observe the changes in the expression of TH protein. Fluoro-Jade B staining was used to detect degeneration and necrosis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) detected the apoptosis of mesencephalic dopaminergic nerve cells. Immunohistochemistry and western blotting showed that the number of TH positive cells and the protein levels in the VTA and SN were significantly decreased in the rats with a long period of morphine dependency. With prolonged morphine exposure, the dopaminergic nerve cells in the VTA and SN showed degeneration and necrosis, while apoptotic cells were not observed. The number of VTA and SN dopaminergic nerve cells decreased with increasing periods of morphine dependence, which was most likely attributable to the degeneration and necrosis of nerve cells induced by morphine toxicity. PMID:26386147

  5. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    PubMed Central

    2012-01-01

    Objective Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments. PMID:23351279

  6. Efficacy of parecoxib, sumatriptan, and rizatriptan in the treatment of acute migraine attacks.

    PubMed

    Müller, Thomas; Lohse, Lutz

    2011-01-01

    Triptans and analgetic nonsteroidal inflammatory drugs reduce acute pain syndromes in migraine. A further treatment option for an acute headache attack in patients with migraine may be the application of cyclooxygenase-2-specific inhibitors, as they have anti-inflammatory and analgesic properties. The objective of this pilot study was to investigate the effects of an oral fast-dissolving tablet of 10 mg of rizatriptan, an intravenous infusion of 40 mg of parecoxib, and a subcutaneous pen injection of sumatriptan (6 mg/0.5 mL) on pain relief in 3 cohorts of patients with episodic migraine. They were treated owing to the acute onset of a pain attack as a case of emergency. They were randomized to treatment with sumatriptan, rizatriptan, or parecoxib. The participants completed a visual analog scale for pain intensity at baseline before the drug administration and then after intervals of 20, 30, 60, and 120 minutes. Rizatriptan, parecoxib, and sumatriptan reduced pain symptoms. Twenty and 30 minutes after drug intake, rizatriptan was more efficacious than parecoxib and sumatriptan, and parecoxib was more effective than sumatriptan. Only a significant difference between rizatriptan and sumatriptan was found after 60 and 120 minutes. This trial demonstrates the effectiveness of a parecoxib infusion in the treatment of acute migraine and that the circumvention of the first pass effect of the liver by rizatriptan may be beneficial for fast pain relief. PMID:21996647

  7. Treatment of mild to moderate pain of acute soft tissue injury: diflunisal vs acetaminophen with codeine.

    PubMed

    Muncie, H L; King, D E; DeForge, B

    1986-08-01

    Acute soft tissue injuries create pain and limitation of function. Treatment requires analgesia and time for full recovery. Acetaminophen with codeine (650 mg plus 60 mg, respectively, every 4 to 6 hours) is used frequently as the analgesic of choice. Diflunisal (1,000 mg initially then 500 mg twice a day) vs acetaminophen with codeine was prospectively studied in the treatment of acute mild to moderate pain from soft tissue injuries. Thirty-five patients with acute strains, sprains, or low back pain were randomized to treatment (17 acetaminophen with codeine vs 18 diflunisal). Both groups were similar in the amount of pain and type of injury at initiation of therapy. Patient pain rating went from 3.3 +/- 0.6 to 1.6 +/- 1.5 for acetaminophen with codeine and from 3.3 +/- 0.6 to 1.3 +/- 1.1 for diflunisal. However, 65 percent of acetaminophen with codeine patients experienced side effects, with 35 percent of these patients stopping the medication because of intolerable side effects. In the diflunisal group, 28 percent of the patients experienced side effects and 5 percent had to stop the medication early. Diflunisal was found to be an effective analgesic in mild to moderate pain of acute soft tissue injuries, and caused fewer and more tolerable side effects than did acetaminophen with codeine. PMID:2942630

  8. Acupuncture Treatment for Acute Ankle Injury in the Emergency Department: A Preliminary Case Report.

    PubMed

    Tantivesruangdet, Nopmanee

    2016-02-01

    Acupuncture is an ancient medical treatment that is increasingly attracting the interest of the public. It is a complementary therapy that is widely used for management of pain, especially chronic discomfort caused by migraine, low-back pain and osteoarthritis of the knee(¹⁻³). The evidence base for the effectiveness of acupuncture and its clinical applications is controversial, and although its efficacy and safety in the management of acute pain have been demonstrated, the quality of this modality is still questionable. The present study reports a case of acute ankle injury, which was treated with acupuncture. A 33-year-old man presented with acute twisted ankle injury. He had pain with swelling around the ankle, and he was experiencing difficulty in walking. His clinical diagnosis was acute ankle sprain with severe pain. Several drug treatments are used for pain control, but in this case, we used acupuncture. After treatment, his pain diminished significantly with a decrease in VAS pain level from 8 to 4 in 20 minutes. At follow-up after one month, we found no skin infection in this case. PMID:27266242

  9. Structure-activity relationships and discovery of a G protein biased μ opioid receptor ligand, [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the treatment of acute severe pain.

    PubMed

    Chen, Xiao-Tao; Pitis, Philip; Liu, Guodong; Yuan, Catherine; Gotchev, Dimitar; Cowan, Conrad L; Rominger, David H; Koblish, Michael; Dewire, Scott M; Crombie, Aimee L; Violin, Jonathan D; Yamashita, Dennis S

    2013-10-24

    The concept of "ligand bias" at G protein coupled receptors has been introduced to describe ligands which preferentially stimulate one intracellular signaling pathway over another. There is growing interest in developing biased G protein coupled receptor ligands to yield safer, better tolerated, and more efficacious drugs. The classical μ opioid morphine elicited increased efficacy and duration of analgesic response with reduced side effects in β-arrestin-2 knockout mice compared to wild-type mice, suggesting that G protein biased μ opioid receptor agonists would be more efficacious with reduced adverse events. Here we describe our efforts to identify a potent, selective, and G protein biased μ opioid receptor agonist, TRV130 ((R)-30). This novel molecule demonstrated an improved therapeutic index (analgesia vs adverse effects) in rodent models and characteristics appropriate for clinical development. It is currently being evaluated in human clinical trials for the treatment of acute severe pain. PMID:24063433

  10. Morphine modulates mouse hippocampal progenitor cell lineages by up-regulating miR-181a level

    PubMed Central

    Xu, Chi; Zhang, Yue; Zheng, Hui; Loh, Horace H.; Law, Ping-Yee

    2014-01-01

    The mechanism by which addictive drugs such as morphine regulate adult neurogenesis remains elusive. We now demonstrate that morphine can regulate neurogenesis by control of miR-181a and subsequent hippocampal neural progenitor cell (hNPC) lineages. In the presence of morphine, hNPCs preferentially differentiated into astrocytes, an effect blocked by the specific μ-opioid receptor antagonist, Cys2-Tyr3-Orn5-Pen7-amide. This effect was mediated by the Prox1/Notch1 pathway as demonstrated by an increase in Notch1 level in the morphine- but not fentanyl-treated hNPCs, and blocked by over-expression of Notch1 siRNA. Over-expression of Prox1 siRNA up-regulated Notch1 level and potentiated the morphine-induced lineage changes. Prox1 transcript level was regulated by direct interaction between miR-181a and its 3′UTR sequence. In vitro and in vivo treatment with morphine resulted in an increase in miR-181a level in hNPCs and mouse hippocampi, respectively. Over-expression of miR-181a mimics reduced Prox1 levels, increased Notch1 levels and enhanced hNPCs differentiation into astrocytes. Meanwhile, over-expression of the miR-181a inhibitor raised Prox1 levels, decreased Notch1 levels and subsequently blocked the morphine-induced lineage changes. Thus, by modulating Prox1/Notch1 activities via miR-181a, morphine influences the fate of differentiating hNPCs differentiation and therefore the ultimate quantities of mature neurons and astrocytes. PMID:24964978

  11. Yokukansan inhibits morphine tolerance and physical dependence in mice: the role of α₂A-adrenoceptor.

    PubMed

    Nakagawa, T; Nagayasu, K; Nishitani, N; Shirakawa, H; Sekiguchi, K; Ikarashi, Y; Kase, Y; Kaneko, S

    2012-12-27

    Yokukansan (YKS) is a traditional Japanese medicine consisting of seven medicinal herbs that is used for the treatment of neurosis, insomnia, and the behavioral/psychological symptoms of dementia. This study examined the effects of YKS on morphine tolerance and physical dependence in mice. Daily oral administration of YKS (0.5 or 1.0 g/kg) for 3 weeks significantly attenuated morphine tolerance and naloxone-precipitated morphine withdrawal signs (jumps and body weight loss) without affecting the analgesic effect of morphine. The inhibitory effect of YKS on withdrawal jumps in morphine-dependent mice was blocked by a single pretreatment with an α(2)-adrenoceptor antagonist, yohimbine, but not by an α(1)-adrenoceptor antagonist, prazosin. A similar inhibitory effect on withdrawal jumps was observed by repeated administration of yohimbine. The membrane expression of α(2A)-adrenoceptors in the pons/medulla was decreased in morphine withdrawn animals; this reduction was prevented by repeated administration of YKS or yohimbine. Competitive radioligand and [(35)S]guanosine-5'-O-(3-thiotriphosphate) binding assays revealed that YKS and its constituent herbs, Glycyrrhiza (GR) and Uncaria hook (UH), had specific binding affinity for and antagonist activity against the α(2A)-adrenoceptor. Certain chemical constituents, including GR -derived glycyrrhizin and its metabolite, 18β-glycyrrhetinic acid, and UH-derived geissoschizine methyl ether (GME), shared such activities. Repeated administration of GR, UH, glycyrrhizin or GME significantly inhibited morphine withdrawal signs. These results suggest that YKS and its active constituents inhibit morphine tolerance and physical dependence, and that the latter is due at least in part to the prevention of the decreased membrane expression of the α(2A)-adrenoceptor in the brainstem by its prolonged blockade. PMID:23069764

  12. Percutaneous cystic duct stent placement in the treatment of acute cholecystitis.

    PubMed

    Comin, Jules M; Cade, Richard J; Little, Andrew F

    2010-10-01

    Percutaneous cholecystostomy is well established as a temporising treatment option in selected patients presenting with acute cholecystitis. However, some patients who undergo cholecystostomy will have persistent discharge, which precludes catheter removal, or may not be medically suitable for future cholecystectomy. In these circumstances, percutaneous cystic duct stenting isa novel treatment option. It may delay or avoid the need for cholecystectomy, and thereby provide definitive treatment in a subset of patients who have acute cholecystitis and a high anaesthetic risk or limited life expectancy. Current application has been limited largely to patients with pre-existing malignant common bile duct strictures, but there is potential for the application to be broadened to include other subsets of patients. In this paper, we describe the technique used for percutaneous cystic duct stenting in a patient and report on its effectiveness. We also explore the technical considerations and consider the application of the procedure on other groups of patients. PMID:20976992

  13. [Open thrombectomy in treatment of acute thromboses of lower-limb deep veins].

    PubMed

    Shaĭdakov, E V; Porembskaia, O Ia; Tsarev, O I; Khmel'niker, S M

    2014-01-01

    Thrombosis of lower-limb deep veins is one of the most common vascular diseases in the world. For a long time the generally accepted treatment policy was conservative therapy with anticoagulants. The article is a review of the literature containing the results of studies carried out over the past two decades and confirming efficacy of surgical treatment for acute venous thrombosis. Presented are the data showing that thrombectomy performed within the first 10-14 days from the onset of the disease, improving quality of life of patients and preventing invalidization thereof. The gained world experience makes it possible to work out the most effective approaches to treatment of acute venous thromboses. PMID:25646547

  14. Effects of Repetitive Hyperbaric Oxygen Treatment in Patients with Acute Cerebral Infarction: A Pilot Study

    PubMed Central

    Chen, Cheng-Hsin; Chen, Shao-Yuan; Wang, Vinchi; Chen, Chao-Ching; Wang, Kaw-Chen; Chen, Chih-Hao; Liu, Yi-Chien; Lu, Kuo-Cheng; Yip, Ping-Keung; Ma, Wen-Ya; Liu, Chuan-Chieh

    2012-01-01

    The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This prospective study assessed the efficacy and safety of HBOT as adjuvant treatment on 46 acute ischemic stroke in patients who did not receive thrombolytic therapy. The HBOT group (n = 16) received conventional medical treatment with 10 sessions of adjunctive HBOT within 3–5 days after stroke onset, while the control group (n = 30) received the same treatment but without HBOT. Early (around two weeks after onset) and late (one month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. The baseline clinical characteristics were similar in both groups. Both early and late outcomes of the HBOT group showed significant difference (P ≤ 0.001). In the control group, there was only significant difference in early outcome (P = 0.004). For early efficacy, there was no difference when comparing changes of NIHSS scores between the two groups (P = 0.140) but there was statistically significant difference when comparing changes of NIHSS scores at one month (P ≤ 0.001). The HBOT used in this study may be effective for patients with acute ischemic stroke and is a safe and harmless adjunctive treatment. PMID:22919348

  15. Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment?

    PubMed

    Safioleas, Konstantinos; Giamarellos-Bourboulis, Evangelos J; Carrer, Dionyssia-Pinelopi; Pistiki, Aikaterini; Sabracos, Lambros; Deliveliotis, Charalambos; Chrisofos, Michael

    2016-05-01

    Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells. PMID:26844659

  16. A Methanol Extract of Brugmansia arborea Affects the Reinforcing and Motor Effects of Morphine and Cocaine in Mice.

    PubMed

    Bracci, Antonio; Daza-Losada, Manuel; Aguilar, Maria; De Feo, Vincenzo; Miñarro, José; Rodríguez-Arias, Marta

    2013-01-01

    Previous reports have shown that several of the effects of morphine, including the development of tolerance and physical withdrawal symptoms, are reduced by extracts of Brugmansia arborea (L.) Lagerheim (Solanaceae) (B. arborea). In the present study we evaluate the action of the methanol extract of B. arborea (7.5-60 mg/kg) on the motor and reinforcing effects of morphine (20 and 40 mg/kg) and cocaine (25 mg/kg) using the conditioned place preference (CPP) procedure. At the doses employed, B. arborea did not affect motor activity or induce any effect on CPP. The extract partially counteracted morphine-induced motor activity and completely blocked the CPP induced by 20 mg/kg morphine. On the other hand, B. arborea blocked cocaine-induced hyperactivity but did not block cocaine-induced CPP. Reinstatement of extinguished preference with a priming dose of morphine or cocaine was also inhibited by B. arborea. The complex mechanism of action of B. arborea, which affects the dopaminergic and the cholinergic systems, seems to provide a neurobiological substrate for the effects observed. Considered as a whole, these results point to B. arborea as a useful tool for the treatment of morphine or cocaine abuse. PMID:23533488

  17. Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway.

    PubMed

    Mao, Mao; Qian, Yanning; Sun, Jie

    2016-04-01

    To investigate the effect of morphine on T helper lymphocyte differentiation and PI3K/AKT pathway mechanism, CD4+ lymphocytes were treated by phorbol-myristate-acetate (25 ng/ml) (PMA) plus ionomycin (1 μg/ml) in the presence of various concentrations of morphine (25, 50, 100, 200 ng/ml) for 4 h. Th1 and Th2 subsets, supernatant cytokines, and PI3K, AKT, and protein kinase C-theta (PKC-θ) levels were detected. The Th1 cell percentage, Th1-derived cytokines, and ratio of Th1/Th2 decreased in the presence of morphine in a concentration-dependent manner. However, Th2 cell percentage kept stable after morphine treatment. The phosphorylation of PI3K and AKT decreased, but the phosphorylation of PKC-θ did not change in the presence of morphine. The decreased percentage of Th1 cells and ratio of Th1/Th2 was recovered by naloxone concentration-dependently. Morphine can inhibit the differentiation of Th1 lymphocytes and decrease the ratio of Th1/Th2 via the pathway of PI3K/AKT. The effect can be inhibited by naloxone. PMID:26883517

  18. Toll-like receptor 4 contributes to the inhibitory effect of morphine on colonic motility in vitro and in vivo.

    PubMed

    Farzi, Aitak; Halicka, Juraj; Mayerhofer, Raphaela; Fröhlich, Esther E; Tatzl, Eva; Holzer, Peter

    2015-01-01

    Opioids rank among the most potent analgesic drugs but gastrointestinal side effects, especially constipation, limit their therapeutic utility. The adverse effects of opioids have been attributed to stimulation of opioid receptors, but emerging evidence suggests that opioids interact with the innate immune receptor Toll-like receptor 4 (TLR4) and its signalling pathway. As TLR4 signalling affects gastrointestinal motility, we examined the involvement of TLR4 in morphine-induced depression of peristaltic motility in the guinea-pig intestine in vitro and male C57BL/6N mice in vivo. While the TLR4 antagonist TAK-242 (0.1 μM and 1 μM) did not alter the morphine-induced inhibition of peristalsis in the isolated guinea-pig small intestine, the morphine-induced decrease in pellet propulsion velocity in colonic segments was attenuated by TAK-242 (0.1 μM). The ability of TAK-242 (4 mg/kg) to mitigate the morphine-induced suppression of colonic motility was replicated in mice in vivo by measuring the expulsion time of beads inserted in the distal colon. The inhibition of upper gastrointestinal transit of mice by morphine was not affected by pre-treatment with TAK-242 (4 mg/kg) in vivo. This is the first report that morphine-induced inhibition of colonic peristalsis is alleviated by TLR4 antagonism. We therefore conclude that TLR4 may contribute to opioid-induced constipation. PMID:25962524

  19. μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster

    PubMed Central

    Garcia-Concejo, Adrian; Jimenez-Gonzalez, Ada; Rodríguez, Raquel E.

    2016-01-01

    Since their discovery, miRNAs have emerged as a promising therapeutical approach in the treatment of several diseases, as demonstrated by miR-212 and its relation to addiction. Here we prove that the miR-212/132 cluster can be regulated by morphine, through the activation of mu opioid receptor (Oprm1). The molecular pathways triggered after morphine administration also induce changes in the levels of expression of oprm1. In addition, miR-212/132 cluster is actively repressing the expression of mu opioid receptor by targeting a sequence in the 3’ UTR of its mRNA. These findings suggest that this cluster is closely related to opioid signaling, and function as a post-transcriptional regulator, modulating morphine response in a dose dependent manner. The regulation of miR-212/132 cluster expression is mediated by MAP kinase pathway, CaMKII-CaMKIV and PKA, through the phosphorylation of CREB. Moreover, the regulation of both oprm1 and of the cluster promoter is mediated by MeCP2, acting as a transcriptional repressor on methylated DNA after prolonged morphine administration. This mechanism explains the molecular signaling triggered by morphine as well as the regulation of the expression of the mu opioid receptor mediated by morphine and the implication of miR-212/132 in these processes. PMID:27380026

  20. Single and Repeated Ultra-Rapid Detoxification Prevents Cognitive Impairment in Morphine Addicted Rats: A Privilege for Single Detoxification

    PubMed Central

    Ghamati, Leila; Hajali, Vahid; Sheibani, Vahid; Esmaeilpour, Khadijeh; Sepehri, Gholamreza; Shojaee, Mojtaba

    2014-01-01

    Background Opioids have been shown to affect learning and memory processes. Different protocols of morphine withdrawal can substantially vary in their success to prevent opioid induced impairments of cognitive performance. In the present study, we report the effects of single and repetitive ultra-rapid detoxification (URD) on spatial learning and memory in morphine addicted rats. Methods Morphine (10 mg/kg) was intraperitoneally (IP) injected in male rats once a day over one week and after which they were detoxified with naloxone administration under anesthesia. For the repetitive procedure, a second one week morphine treatment with a second subsequent detoxification was performed. Control groups received an equivalent volume of saline injections. Spatial learning and memory was evaluated using the Morris water maze (MWM) task. Findings Both protocols of morphine administration resulted in a severe spatial memory impairment that could be significantly prevented by both single and repetitive URD. However, memory abilities in animals treated with repetitive URD were still significantly lower than in animals of the corresponding control group. Alterations in motor activity or sensory-motor coordination between morphine treated and control animals could be ruled out by comparing swimming speed and visible platform performances that were not different between groups. Thus, URD and, specifically single URD, can prevent the spatial memory impairments in addicted rats. Conclusion As opioid addiction is an extending and serious concern in many societies, these findings may have clinical values and therapeutic implications for patients who experience multiple opioid relapses. PMID:25140218