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1.
Pharmacol Rep ; 70(3): 565-569, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29679880

ABSTRACT

BACKGROUND: We aimed to evaluate the effect of doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. METHODS: After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of doxylamine, we assessed doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. RESULTS: We demonstrated that doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED50)), the relative potency was bupivacaine (0.41 (0.36-0.48) mmol)> doxylamine (7.39 (6.91-7.91)mmol) (p<0.01). On an equipotent basis (ED25, ED50 and ED75), subcutaneous doxylamine resulted in greater duration of action (p<0.01) than bupivacaine at producing cutaneous analgesia. CONCLUSIONS: The result of this experiment indicated that doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose.


Subject(s)
Anesthetics, Local/administration & dosage , Doxylamine/administration & dosage , Administration, Cutaneous , Analgesia/methods , Animals , Bupivacaine/administration & dosage , Dose-Response Relationship, Drug , Injections, Subcutaneous/methods , Male , Pain/drug therapy , Rats , Rats, Sprague-Dawley , Skin/metabolism
2.
Biomed Pharmacother ; 101: 155-161, 2018 May.
Article in English | MEDLINE | ID: mdl-29486333

ABSTRACT

Animal models are widely used to develop drugs for treating diabetes mellitus (DM). Insulin resistance (IR) is one of the main problems in type-2 DM (T2DM). Streptozotocin (STZ) is used to damage pancreatic cells for induction of DM. Many rat models were applied in research as T2DM. However, the degree of IR in each model is unknown. In the present study, IR and insulin signaling were compared in four models of type 2 diabetes: rats fed a fructose-rich chow for 8 weeks, rats feed high-fat chow for 4 weeks followed by injection with streptozotocin (35 mg/kg, i.p.), rats injected with a single low dose streptozotocin (45 mg/kg, i.p.), and rats injected with a single dose of nicotinamide followed by a single high dose of streptozotocin (60 mg/kg, i.p.). Values from these determinations in diabetic rats showing the order that insulin resistance is most marked in rats received fructose-rich chow followed by high-fat diet before STZ injection induced model (HFD/STZ rats), and rats injected with low dose of STZ but it is less marked in rats induced by nicotinamide and STZ. Additionally, insulin secretion was reduced in three rat models except the rats receiving fructose-rich chow. Western blots also showed the same changes in phosphorylation of IRS-1 or Akt using soleus muscle from each model. The obtained data suggest a lack of pronounced IR in the rats with acute diabetes induced by nicotinamide and STZ while IR is markedly identified in rats fed fructose-rich chow. However, the increase of plasma glucose levels in fructose-rich chow-fed rats was not so significant as other groups. Therefore, HFD/STZ rats is an appropriate and stable animal model which is analogous to the human T2DM through a combination of high-fat diet with multiple low-dose STZ injections.


Subject(s)
Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Insulin Resistance/physiology , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/etiology , Diabetes Mellitus, Type 2/etiology , Diet, High-Fat/adverse effects , Dietary Fats/adverse effects , Dietary Fats/toxicity , Fructose/toxicity , Male , Rats , Rats, Sprague-Dawley , Streptozocin/toxicity
3.
Fundam Clin Pharmacol ; 31(6): 636-642, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28677297

ABSTRACT

We aimed to investigate the local anesthetic properties of naloxone alone or as an adjunct for the local anesthetic lidocaine. After the block of the cutaneous trunci muscle reflex (CTMR) with drugs delivery by subcutaneous infiltration, cutaneous nociceptive block was tested on the ratsꞌ backs. We demonstrated that naloxone, as well as lidocaine, elicited cutaneous analgesia dose-dependently. The relative potency in inducing cutaneous analgesia was lidocaine [22.6 (20.1 - 25.4) µmol/kg] > naloxone [43.2 (40.3 - 46.4) µmol/kg] (P < 0.05). On an equianesthetic basis [50% effective dose (ED50 ), ED25 , and ED75 ], naloxone displayed a greater duration of cutaneous analgesic action than lidocaine (P < 0.01). Coadministration of lidocaine (ED95 or ED50 ) and ineffective-dose naloxone (13.3 µmol/kg) intensifies sensory block (P < 0.01) with prolonged duration of action (P < 0.001) compared with lidocaine (ED95 or ED50 ) alone or naloxone (13.3 µmol/kg) alone on infiltrative cutaneous analgesia. The preclinical data showed that naloxone is less potent than lidocaine as an infiltrative anesthetic, but its analgesic duration was longer than that of lidocaine. Furthermore, naloxone prolongs lidocaine analgesia, acting synergistically for nociceptive block.


Subject(s)
Anesthetics, Local/therapeutic use , Lidocaine/therapeutic use , Naloxone/therapeutic use , Pain/prevention & control , Anesthetics, Local/administration & dosage , Anesthetics, Local/pharmacology , Animals , Dose-Response Relationship, Drug , Lidocaine/administration & dosage , Lidocaine/pharmacology , Male , Naloxone/administration & dosage , Naloxone/pharmacology , Nociceptors/drug effects , Pain Measurement , Random Allocation , Rats , Rats, Sprague-Dawley
4.
J Funct Biomater ; 8(1)2017 Jan 26.
Article in English | MEDLINE | ID: mdl-28134777

ABSTRACT

The anti-inflammatory and vasodilating effects of three selected dietary organic sulfur compounds (OSC), including diallyl disulfide (DADS), dimethyl disulfide (DMDS), and propyl disulfide (PDS), from Allium species were investigated. In the anti-inflammatory activity assay, the three OSC demonstrated significant inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-induced RAW 264.7 cells. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in activated RAW 264.7 cells was inhibited by the three OSC, indicating that the three OSC prevented the LPS-induced inflammatory response in RAW 264.7 cells. For the vasodilative assay, the three OSC were ineffective in producing NO in SVEC4-10 cells, but they did enhance prostacyclin (PGI2) production. The expression of COX-2 in SVEC4-10 cells was activated by DADS and DMDS. Pretreatment of SVEC4-10 cells with the three OSC decreased ROS generation in H2O2-induced SVEC4-10 cells. In addition, the three OSC significantly inhibited angiotensin-I converting enzyme (ACE). The up-regulation of PGI2 production and COX-2 expression by DADS and DMDS and the reduction of ROS generation by DADS, DMDS, and PDS in SVEC4-10 cells contributed to the vasodilative effect of the three OSC. Collectively, these findings suggest that DADS, DMDS, and PDS are potential anti-inflammatory and vasodilative mediators.

5.
J Neurosurg ; 124(6): 1654-64, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26613168

ABSTRACT

OBJECT Hypoxia can induce cell death or trigger adaptive mechanisms to guarantee cell survival. Neuron-derived orphan receptor 1 (NOR-1) works as an early-response protein in response to a variety of environmental stresses. In this study, the authors evaluated the roles of NOR-1 in hypoxia-induced neuronal insults. METHODS Neuro-2a cells were exposed to oxygen/glucose deprivation (OGD). Cell viability, cell morphology, cas-pase-3 activity, DNA fragmentation, and cell apoptosis were assayed to determine the mechanisms of OGD-induced neuronal insults. RNA and protein analyses were carried out to evaluate the effects of OGD on expressions of NOR-1, cAMP response element-binding (CREB), and cellular inhibitor of apoptosis protein 2 (cIAP2) genes. Translations of these gene expressions were knocked down using RNA interference. Mice subjected to traumatic brain injury (TBI) and NOR-1 was immunodetected. RESULTS Exposure of neuro-2a cells to OGD decreased cell viability in a time-dependent manner. Additionally, OGD led to cell shrinkage, DNA fragmentation, and cell apoptosis. In parallel, treatment of neuro-2a cells with OGD time dependently increased cellular NOR-1 mRNA and protein expressions. Interestingly, administration of TBI also augmented NOR-1 levels in the impacted regions of mice. As to the mechanism, exposure to OGD increased nuclear levels of the transcription factor CREB protein. Downregulating CREB expression using RNA interference simultaneously inhibited OGD-induced NOR-1 mRNA expression. Also, levels of cIAP2 mRNA and protein in neuro-2a cells were augmented by OGD. After reducing cIAP2 translation, OGD-induced cell death was reduced. Sequentially, application of NOR-1 small interfering RNA to neuro-2a cells significantly inhibited OGD-induced cIAP2 mRNA expression and concurrently alleviated hypoxia-induced alterations in cell viability, caspase-3 activation, DNA damage, and cell apoptosis. CONCLUSIONS This study shows that NOR-1 can transduce survival signals in neuronal cells responsible for hypoxiainduced apoptotic insults through activation of a CREB/cIAP2-dependent mechanism.


Subject(s)
Apoptosis/physiology , Cell Hypoxia/physiology , DNA-Binding Proteins/metabolism , Glucose/deficiency , Hypoxia/physiopathology , Nerve Tissue Proteins/metabolism , Neurons/physiology , Receptors, Steroid/metabolism , Receptors, Thyroid Hormone/metabolism , Animals , Caspase 3/metabolism , Cell Line, Tumor , Cell Survival/physiology , Cyclic AMP Response Element-Binding Protein/metabolism , Disease Models, Animal , Male , Mice , Mice, Inbred ICR , RNA, Messenger/metabolism
6.
Anesthesiology ; 123(1): 136-47, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25955981

ABSTRACT

BACKGROUND: The effects of the mode of anesthesia on major adverse postoperative outcomes in geriatric patients are still inconclusive. The authors hypothesized that a neuraxial anesthetic (NA) rather than a general anesthetic (GA) would yield better in-hospital postoperative outcomes for geriatric patients undergoing hip surgery. METHODS: The authors used data from Taiwan's 1997-2011 in-patient claims database to evaluate the effect of anesthesia on in-hospital outcomes. The endpoints were mortality, stroke, transient ischemic stroke, myocardial infarction, respiratory failure, and renal failure. Of the 182,307 geriatric patients who had hip surgery, a GA was given to 53,425 (29.30%) and an NA to 128,882 (70.70%). To adjust for baseline differences and selection bias, patients were matched on propensity scores, which left 52,044 GA and 52,044 NA patients. RESULTS: GA-group patients had a greater percentage and higher odds of adverse in-hospital outcomes than did NA-group patients: death (2.62 vs. 2.13%; odds ratio [OR], 1.24; 95% CI, 1.15 to 1.35; P < 0.001), stroke (1.61 vs. 1.38%; OR, 1.18, 95% CI, 1.07 to 1.31; P = 0.001), respiratory failure (1.67 vs. 0.63%; OR, 2.71; 95% CI, 2.38 to 3.01; P < 0.001), and intensive care unit admission (11.03 vs. 6.16%; OR, 1.95; 95% CI, 1.87 to 2.05; P < 0.001), analyzed using conditional logistic regression. Moreover, patients given a GA had longer hospital stays (10.77 ± 8.23 vs. 10.44 ± 6.67 days; 95% CI, 0.22 to 0.40; P < 0.001) and higher costs (New Taiwan Dollars [NT$] 86,606 ± NT$74,162 vs. NT$74,494 ± NT$45,264; 95% CI, 11,366 to 12,859; P < 0.001). CONCLUSION: For geriatric patients undergoing hip surgery, NA was associated with fewer odds of adverse outcomes than GA.


Subject(s)
Anesthesia, General/adverse effects , Anesthesia, Spinal/adverse effects , Arthroplasty, Replacement, Hip , Population Surveillance , Postoperative Complications/diagnosis , Propensity Score , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Postoperative Complications/epidemiology , Treatment Outcome
7.
Eur J Pharmacol ; 722: 48-54, 2014 Jan 05.
Article in English | MEDLINE | ID: mdl-24184695

ABSTRACT

Glucocorticoids, used primarily as anti-allergic and anti-inflammatory drugs, are also effective, alone or combined with other antiemetics, for preventing nausea and vomiting. Dexamethasone, one of the glucocorticoids, has been suggested as a first-line drug for preventing low-level emetogenic chemotherapy- and radiotherapy-induced nausea and vomiting, and in patients with only one or two risks for postoperative nausea and vomiting (PONV). Dexamethasone combined with 5-HT3 or tachykinin NK1 antagonists is also suggested for higher-level emetogenic chemotherapy and radiotherapy and for patients at high risk for PONV. Glucocorticoids may act via the following mechanisms: (1) anti-inflammatory effect; (2) direct central action at the solitary tract nucleus, (3) interaction with the neurotransmitter serotonin, and receptor proteins tachykinin NK1 and NK2, alpha-adrenaline, etc.; (4) maintaining the normal physiological functions of organs and systems; (5) regulation of the hypothalamic-pituitary-adrenal axis; and (6) reducing pain and the concomitant use of opioids, which in turn reduces opioid-related nausea and vomiting.


Subject(s)
Antiemetics/pharmacology , Dexamethasone/pharmacology , Glucocorticoids/pharmacology , Vomiting/drug therapy , Antiemetics/therapeutic use , Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Humans , Nausea/chemically induced , Nausea/drug therapy , Nausea/etiology , Nausea/metabolism , Nausea/microbiology , Vomiting/chemically induced , Vomiting/etiology , Vomiting/metabolism
8.
Eur J Pharmacol ; 702(1-3): 20-4, 2013 Feb 28.
Article in English | MEDLINE | ID: mdl-23353594

ABSTRACT

The best analgesic drugs for neuropathic pain have a long duration of action, can be given via multiple routes, and can be used preemptively. We evaluated the antinociceptive effects and duration of action of subcutaneously injected amitriptyline base (AMT-Base) (in oil). A plantar test in a spinal nerve ligation (SNL) model of neuropathic pain in rats showed that typical amitriptyline HCl (AMT-HCl) (in saline) and AMT-Base had a significant dose-dependent antinociceptive effect: the antinociceptive duration of a single 100 µmol/kg injection of AMT-HCl was 5 h and of AMT-Base was 24 h when given 7 days after a SNL, and of a single 200 µmol/kg injection of AMT-Base was 39 days when given 1 h before and 4 days when given 7 days after a SNL. The post-ligation antinociceptive duration of AMT-Base was 4.8 times that of AMT-HCl, but the duration of preemptive (pre-ligation) AMT-Base treatment was 9.7 times that of AMT-Base. We can conclude that preemptive amitriptyline base provides long-lasting antinociception for neuropathic pain experimentally.


Subject(s)
Amitriptyline/therapeutic use , Analgesics/therapeutic use , Hyperalgesia/drug therapy , Neuralgia/drug therapy , Animals , Disease Models, Animal , Ligation , Male , Rats , Rats, Sprague-Dawley , Spinal Nerves/surgery
9.
Eur J Pharmacol ; 693(1-3): 25-30, 2012 Oct 15.
Article in English | MEDLINE | ID: mdl-22935636

ABSTRACT

The purpose of the study is to find subcutaneous equianalgesic doses of memantine, amantadine and bupivacaine and use these doses to quantify the cardiovascular and central nervous system toxicity of these agents after intravenous administration. Memantine, amantadine and bupivacaine, a local anesthetic, in a dose-related fashion were determined for cutaneous analgesia by a block of the cutaneous trunci muscle reflex in rats, and equipotent doses were calculated. Following rapid intravenous infusion of equianalgesic bupivacaine, memantine, amantadine and saline (vehicle) in rats, we observed the onset time of seizure, apnea and impending death, and monitored mean arterial blood pressure and heart rate. Memantine and amantadine elicited dose-dependent cutaneous analgesia. At the 50% effective dose (ED(50)), the rank of potencies was bupivacaine [1.8 (1.7-2.0)]>memantine [19.1 (17.6-21.8)]>amantadine [36.1 (32.0-40.3)] (P<0.05). On ED(25), ED(50) and ED(75) basis, the duration caused by bupivacaine was similar to that caused by memantine or amantadine. At equianalgesic doses, the infusion time of memantine or amantadine required to induce seizure, impending death, and apnea was longer than that of bupivacaine during rapid intravenous infusion (P<0.01). The decreasing slope in mean arterial blood pressure and heart rate was slower with memantine and amantadine when compared with bupivacaine at equivalent doses (P<0.01). Our data showed that memantine and amantadine (i) were equal to bupivacaine at producing durations of cutaneous analgesia but (ii) were less likely than bupivacaine to cause cardiovascular and central nervous system toxicity.


Subject(s)
Amantadine/administration & dosage , Analgesia/methods , Analgesics, Non-Narcotic/administration & dosage , Anesthetics, Local/administration & dosage , Memantine/administration & dosage , Amantadine/toxicity , Analgesics, Non-Narcotic/toxicity , Anesthetics, Local/toxicity , Animals , Apnea/chemically induced , Behavior, Animal/drug effects , Blood Pressure/drug effects , Heart Rate/drug effects , Injections, Subcutaneous , Male , Memantine/toxicity , Rats , Rats, Sprague-Dawley , Seizures/chemically induced , Skin/drug effects
10.
Pharmacology ; 87(5-6): 257-64, 2011.
Article in English | MEDLINE | ID: mdl-21494057

ABSTRACT

BACKGROUND/AIMS: The role of opioid receptors in the regulation of vascular function remains unclear. In the current study, we evaluated the ability of loperamide, a peripheral opioid receptor agonist, to regulate blood pressure in spontaneously hypertensive rats (SHRs) and examined the mechanism(s) by which loperamide exerts its effects. METHODS: In male SHRs, mean arterial pressure (MAP) was measured and hemodynamic analysis was recorded. Additionally, the isometric tension of aortic rings isolated from SHRs was determined. RESULTS: Loperamide dose-dependently decreased MAP in SHRs but not in the normal group of Wistar-Kyoto rats. This reduction of MAP in conscious SHRs was abolished by the selective opioid µ-receptor antagonist cyprodime, but not by naloxonazine, the µ(1)-opioid receptor antagonist. However, cardiac output was not altered by loperamide in anesthetized SHRs. Moreover, loperamide-induced relaxation in isolated aortic rings precontracted with phenylephrine or vasopressin. This relaxation was abolished by cyprodime, but not by naloxonazine. Loperamide-induced relaxation was also attenuated by glibenclamide, an ATP-sensitive potassium (K(ATP)) channel blocker. Additionally, vasodilatation by loperamide was reduced by an inhibitor of protein kinase A (PKA) and enhanced by an inhibitor of phosphodiesterases. CONCLUSION: We suggest that loperamide can lower MAP in SHRs via µ(2)-opioid receptor-dependent cAMP-PKA pathway that induces vascular relaxation by opening K(ATP) channels.


Subject(s)
Arteries/physiology , Blood Pressure/physiology , Receptors, Opioid, mu/physiology , Animals , Arteries/drug effects , Arteries/metabolism , Blood Pressure/drug effects , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/metabolism , Endothelium/metabolism , Glyburide/pharmacology , Hemodynamics/drug effects , Intracellular Signaling Peptides and Proteins/pharmacology , KATP Channels/antagonists & inhibitors , KATP Channels/metabolism , Loperamide/pharmacology , Male , Morphinans/pharmacology , Naloxone/analogs & derivatives , Naloxone/pharmacology , Phenylephrine/pharmacology , Phosphodiesterase Inhibitors/pharmacology , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Receptors, Opioid, mu/antagonists & inhibitors , Receptors, Opioid, mu/metabolism , Vasodilation/drug effects
11.
Br J Nutr ; 106(5): 700-7, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21473799

ABSTRACT

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). The aim of the present study was to compare the nutritional status of PHN patients with that of healthy controls, and then to identify risk factors for PHN using multivariate multiple logistic regressions. In the present cross-sectional study, we prospectively enrolled fifty PHN patients for at least 3 months and fifty healthy controls. We selected nine circulating nutrients including ionised Ca, Zn, retinol, folic acid, vitamin B12, vitamin C, α-tocopherol, γ-tocopherol and lycopene associated with both immunity and the modulation of neuropathic pain, and measured their concentrations in plasma/serum. Concentrations of ionised Ca, Zn, vitamin C and vitamin B12 were significantly lower in PHN patients than in controls after excluding those patients receiving supplements since the outbreak of HZ. The prevalence of either mild/marginal or severe deficiencies for any of the nine selected circulating nutrients in PHN patients (92 %) was much higher than that in controls (46 %) (P < 0·001). Lower concentrations of vitamin C ( ≤ 45·0 µmol/l), ionised Ca ( ≤ 1·05 mmol/l) and Zn ( ≤ 0·91 g/l) were found to increase independently the risk of PHN using binary variable (dichotomy) analyses with both PHN patients and controls in a multivariate logistic regression analysis. No significant correlations existed between the risks of PHN and the concentrations of retinol, folic acid, vitamin B12, lycopene or α:γ-tocopherol ratios. Thus, lower concentrations of circulating nutrients, namely vitamin C, ionised Ca or Zn, are probably a risk factor in Taiwanese patients with PHN.


Subject(s)
Deficiency Diseases/epidemiology , Neuralgia, Postherpetic/complications , Aged , Case-Control Studies , Deficiency Diseases/complications , Female , Humans , Male , Middle Aged , Multivariate Analysis , Risk Factors , Specimen Handling , Taiwan/epidemiology
12.
J Agric Food Chem ; 59(8): 3747-53, 2011 Apr 27.
Article in English | MEDLINE | ID: mdl-21391677

ABSTRACT

Catalpol is one of the active principles from roots of Rehmannia glutinosa Steud (Scrophulariaceae) that is widely used to treat diabetic disorders in Chinese traditional medicine using the name of Di-Huang, which is used to investigate the mechanisms for lowering of plasma glucose in streptozotocin-induced diabetic rats (STZ-diabetic rats). Catalpol decreased plasma glucose in a dose-related manner, and this action was reduced by pretreatment with naloxone or naloxonazine. An increase of plasma ß-endorphin by catalpol was also observed in parallel. The plasma glucose lowering action of catalpol was deleted in bilateral adrenalectomized rats. Moreover, catalpol enhanced ß-endorphin release from the isolated adrenal medulla of STZ-diabetic rats. Otherwise, plasma glucose lowering action of catalpol failed to produce in opioid µ-receptor knockout mice. Also, repeated administration of catalpol for 3 days in STZ-diabetic rats resulted in a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. These effects were also reversed by blockade of opioid µ-receptors. Our results suggested that catalpol increased glucose utilization through increase of ß-endorphin secretion from adrenal gland in STZ-diabetic rats.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/therapeutic use , Iridoid Glucosides/therapeutic use , Plant Roots/chemistry , Rehmannia/chemistry , Animals , Diabetes Mellitus, Experimental/blood , Mice , Mice, Knockout , Rats , Rats, Wistar , Streptozocin
13.
Behav Pharmacol ; 21(5-6): 523-9, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20679893

ABSTRACT

Long-term use of morphine can cause neuronal dystrophic changes in specific areas of the brain. These changes may underlie the mechanism for developing morphine antinociceptive tolerance and physical dependence. We evaluated the effect of tianeptine, an antidepressant with prominent neuroprotective and neuroplastic properties, on the development of morphine antinociceptive tolerance and physical dependence. Male C57BL/6 mice were rendered tolerant to or dependent on morphine by subcutaneously injecting them with morphine (10 mg/kg) and intraperitoneally with saline or tianeptine (1, 3, or 5 mg/kg) twice daily for 6 days. The mice were given a daily tail-flick test 1 h after the first morphine injection to evaluate the development of their tolerance to morphine antinociception. To evaluate their physical dependence on morphine, 3 h after the final morphine injection on day 6, naloxone-HCl-precipitated (2 mg/kg, intraperitoneally) withdrawal symptoms were counted for 30 min, and body weight was checked 1 h after the naloxone injection. Tianeptine per se produced no antinociception, neither did it modify the antinociception produced by morphine, nor did it evoke the behavioral responses different from those in the saline controls. The combination of tianeptine with morphine significantly reduced the development of morphine antinociceptive tolerance and suppressed the incidence of naloxone-precipitated withdrawal symptoms. We conclude that tianeptine is an effective inhibitor of morphine-induced antinociceptive tolerance and physical dependence in mice. Our results would imply that comedication with tianeptine and morphine might benefit those who need long-term morphine treatment.


Subject(s)
Drug Tolerance , Morphine Dependence/prevention & control , Morphine/pharmacology , Thiazepines/pharmacology , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/pharmacology , Animals , Antidepressive Agents, Tricyclic/administration & dosage , Antidepressive Agents, Tricyclic/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred C57BL , Morphine/administration & dosage , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Pain/drug therapy , Substance Withdrawal Syndrome/physiopathology , Thiazepines/administration & dosage
14.
Acta Anaesthesiol Taiwan ; 48(1): 3-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20434106

ABSTRACT

BACKGROUND: Local anesthetics exert their anesthetic and analgesic effects by blocking the sodium channels in the nervous system. Phenothiazine-type antipsychotics also block sodium channels, but the local anesthetic characteristics of these drugs have not been evaluated. The aim of this study was to evaluate the cutaneous analgesic effect of phenothiazine-type antipsychotics. METHODS: Using a subcutaneous injection model in rats, we tested the cutaneous analgesic effects of six phenothiazine-type antipsychotics (mesoridazine, promazine, chlorpromazine, fluphenazine, perphenazine and triflupromazine) at a dose of 0.6 mumol, and compared them with those of bupivacaine and lidocaine. A saline injection was used as the control. RESULTS: All six phenothiazine-type antipsychotics elicited cutaneous analgesia. At the dose of 0.6 mumol, the potencies of mesoridazine and promazine were similar to that of bupivacaine; the other four drugs were less potent (p<0.001 for each comparison). Mesoridazine had a longer duration of action than bupivacaine (p<0.001). In terms of ED(50) values, mesoridazine was more potent and longer-acting than bupivacaine and lidocaine (p<0.01 for each comparison). CONCLUSION: Of the antipsychotic drugs tested, mesoridazine is potentially the best candidate for development into a potent, long-acting local anesthetic. However, toxicity studies are needed before these agents can be used clinically as analgesics.


Subject(s)
Anesthetics, Local/pharmacology , Antipsychotic Agents/pharmacology , Phenothiazines/pharmacology , Analgesia , Animals , Dose-Response Relationship, Drug , Male , Rats , Rats, Sprague-Dawley , Sodium Channel Blockers/pharmacology
15.
J Proteome Res ; 9(2): 936-44, 2010 Feb 05.
Article in English | MEDLINE | ID: mdl-20000655

ABSTRACT

Tianeptine, an atypical tricyclic antidepressant with unique characteristics, can improve memory and prevent stress-induced hippocampal damage. It has neuroplastic and neurotrophic effects on hippocampal neurons and can prevent dendritic atrophy of the hippocampus in certain pathological conditions. To obtain a better understanding of the underlying mechanisms, we performed a proteomic analysis on tianeptine-treated hippocampal neurons. Primary hippocampal neurons were prepared from fetal Sprague-Dawley rats, eliminating glia cells by addition of cytosine beta-D-arabinofuranoside at day 2 in vitro (DIV2). The neurons were treated with tianeptine (10 microg/mL) or vehicle at DIV3, then harvested at DIV4 or DIV9 for immunocytochemical analysis of, respectively, neurite outgrowth or synapse formation. A proteomics analysis was performed on DIV4 neurons and the data were confirmed by Western blot analysis. Using specific markers, we demonstrated that tianeptine can augment neurite growth and promote synaptic contacts in cultured hippocampal neurons. The proteomics analysis identified 11 differentially expressed proteins, with roles in neurite growth, metabolism of neurotrophic substances, synaptogenesis, and synaptic activity homeostasis. The data shed light on the mechanisms underlying the neurotrophic effect of tianeptine observed in both animal studies and the clinic.


Subject(s)
Hippocampus/drug effects , Neurons/drug effects , Neuroprotective Agents/pharmacology , Proteomics , Thiazepines/pharmacology , Animals , Electrophoresis, Gel, Two-Dimensional , Female , Hippocampus/cytology , Hippocampus/metabolism , Immunohistochemistry , Nerve Tissue Proteins/metabolism , Pregnancy , Rats , Rats, Sprague-Dawley , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
16.
Acta Pharmacol Sin ; 30(9): 1227-36, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19730427

ABSTRACT

AIM: To assess whether epinephrine, phenylephrine, and methoxamine act via certain subtypes of adrenoceptors to exert their local anesthetic activity. METHODS: We investigated cutaneous anesthesia from adrenoceptor agonists and/or antagonists in conscious, unanesthetized Sprague-Dawley male rats (weight 200-250 g). Cutaneous anesthesia was evidenced by a block of the cutaneous trunci muscle reflex, which is characterized by reflex movement of the skin over the back produced by twitches of lateral thoracispinal muscles in response to local dorsal cutaneous noxious pinprick. RESULTS: Local infiltration of epinephrine, L-phenylephrine, or methoxamine alone induces cutaneous anesthesia in rats in a dose-dependent way. Epinephrine is found to be 19 and 29 times more potent than those of methoxamine and L-phenylephrine, respectively. The cutaneous anesthesia induced by epinephrine, phenylephrine, or methoxamine can be significantly reduced by alpha(1)-adrenoceptor antagonists (eg, prazosin), alpha1, alpha2-adrenoceptor antagonist, alpha(1A)-adrenoceptor antagonist (eg, 5-methylurapdil), alpha(1B)-adrenoceptor antagonist (eg, chloroethylclonidine), or alpha(1D)-adrenoceptor antagonist (eg, BMY7873). CONCLUSION: Our results indicate that epinephrine, phenylephrine and methoxamine all act mainly via mixed subtypes of alpha(1)-adrenoceptors to induce cutaneous anesthesia in the rat.


Subject(s)
Anesthetics, Local/pharmacology , Epinephrine/pharmacology , Methoxamine/pharmacology , Phenylephrine/pharmacology , Receptors, Adrenergic, alpha-1/drug effects , Adrenergic alpha-1 Receptor Antagonists , Anesthesia, Local , Animals , Clonidine/analogs & derivatives , Clonidine/pharmacology , Dose-Response Relationship, Drug , Male , Nifedipine/pharmacology , Nitroglycerin/pharmacology , Pain Measurement/drug effects , Phentolamine/pharmacology , Piperazines/pharmacology , Prazosin/pharmacology , Rats , Rats, Sprague-Dawley
17.
Acta Anaesthesiol Taiwan ; 47(1): 3-9, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19318293

ABSTRACT

BACKGROUND: A combination of antiemetic drugs could be an effective method to prevent severe postoperative nausea and vomiting (PONV). Therefore, we examined the prophylactic effect of haloperidol plus ondansetron on PONV. METHODS: We enrolled 210 patients (n = 70 in each of 3 groups) undergoing elective laparoscopic cholecystectomy for this randomized double-blind study. Patients were randomized to intravenous saline 2 mL and intramuscular haloperidol 2 mg (Group H), intravenous ondansetron 4 mg and intramuscular saline 2 mL (Group O), or intravenous ondansetron 4 mg and intramuscular haloperidol 2 mg (Group H+O), administered after induction of general anesthesia and 30 minutes before the conclusion of surgery. We compared the complete response rates, incidence of PONV, nausea scores, the need for rescue medication, patient satisfaction scores, and adverse events during the 24-hour study. RESULTS: The H+O group had the highest complete response rate to treatment (79%) compared with group H (61%) and group O (62%) (p < 0.05 for both). Patient satisfaction scores were significantly higher in the H+O group (8.3 +/- 1.8) than in the H (7.0 +/- 2.4) and O (7.2 +/- 2.5) groups (p < 0.05 for both). In addition, nausea scores were significantly lower in the H+O group (1.2 +/- 2.6) than in the H (2.5 +/- 3.3) and O (2.2 +/- 3.1) groups (p < 0.05 for both). CONCLUSION: We conclude that the combination of prophylactic haloperidol (2 mg) plus ondansetron (4 mg) provides a higher complete response rate and greater patient satisfaction after laparoscopic cholecystectomy than either drug used alone.


Subject(s)
Antiemetics/administration & dosage , Cholecystectomy, Laparoscopic , Haloperidol/administration & dosage , Ondansetron/administration & dosage , Postoperative Nausea and Vomiting/prevention & control , Adult , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Injections, Intramuscular , Injections, Intravenous , Male
18.
Anesth Analg ; 106(5): 1402-6, table of contents, 2008 May.
Article in English | MEDLINE | ID: mdl-18420851

ABSTRACT

BACKGROUND: Haloperidol, a major tranquilizer, has been found to have a potent antiemetic effect on postoperative nausea and vomiting (PONV), but the prophylactic effect of haloperidol plus dexamethasone on PONV has not been evaluated. We evaluated the prophylactic effect of haloperidol plus dexamethasone to either given alone, placebo or droperidol on PONV in patients undergoing a laparoscopic-assisted vaginal hysterectomy. METHODS: Four hundred adult women (n = 80 in each of five groups) scheduled for a laparoscopic-assisted vaginal hysterectomy were enrolled in a randomized, double-blind, placebo, and positive-control study. Fifteen minutes after the induction of anesthesia, patients received an i.v. injection of either saline (group S), droperidol 1.25 mg (group D), haloperidol 2 mg (group H), dexamethasone 5 mg (group Dx), or haloperidol 2 mg plus dexamethasone 5 mg (group H + Dx) to prevent PONV. The occurrence of PONV and medication-related side effects were recorded. RESULTS: The incidences of PONV (0-24 h) in the D (36%), H (37%), Dx (38%), and H + Dx (19%) groups were significantly lower than in the S group (65%; P < 0.05 for each comparison). The H + Dx group had the lowest incidence of PONV (19%; P < 0.05 for each comparison) of the five study groups. No differences were found between the D, H, and Dx groups. Also, no differences were found among the five groups in the side effects of QT prolongation, intensity of postoperative pain, level of sedation, and occurrence of extra-pyramidal symptoms. CONCLUSION: Prophylactic haloperidol 2 mg plus dexamethasone 5 mg produced a greater reduction in the incidence of PONV than did either drug used alone, placebo or droperidol without increasing perioperative adverse outcomes.


Subject(s)
Antiemetics/therapeutic use , Dexamethasone/therapeutic use , Haloperidol/therapeutic use , Hysterectomy, Vaginal/methods , Laparoscopy , Postoperative Nausea and Vomiting/prevention & control , Adult , Antiemetics/adverse effects , Dexamethasone/adverse effects , Double-Blind Method , Droperidol/therapeutic use , Drug Therapy, Combination , Female , Haloperidol/adverse effects , Humans , Incidence , Middle Aged , Postoperative Nausea and Vomiting/epidemiology , Treatment Outcome
19.
Acta Anaesthesiol Taiwan ; 45(4): 233-6, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18251245

ABSTRACT

"Piton-S", a preparation of synthetic hormone of oxytocin, is the most common pharmacologic agent used for the induction and augmentation of labor, as well as preventing postpartum hemorrhage owing to its uterotonic properties. There are many adverse effects reported with oxytocin, including hypotension and tachycardia. Anaphylactoid reaction to oxytocin is extremely rare. Here we bring forth a case who sustained from anaphylactoid shock following oxytocin administration during the act of cesarean section. We would like to discuss the proper management of perioperative anaphylaxis after review of similar cases in the literature.


Subject(s)
Anaphylaxis/chemically induced , Oxytocin/adverse effects , Adult , Anaphylaxis/diagnosis , Anaphylaxis/therapy , Female , Humans , Pregnancy
20.
J Infect ; 52(2): 118-23, 2006 Feb.
Article in English | MEDLINE | ID: mdl-15904960

ABSTRACT

OBJECTIVES: Laryngoscope blades are in close contact with mucous membranes and can possibly contaminated with virulent or readily transmissible organisms. As laryngoscopy is often required during endotracheal intubation, proper cleaning and sterilization of the laryngoscope blade is crucial to prevent cross-contamination among patients. METHODS: We tested the effectiveness of latex condom using as a laryngoscope blade cover during endotracheal intubation. Both control (no condom) and study group blades were rinsed with sterile saline after intubation. The rinse was sent for bacteria culture, and appearance of bacterial colonization was counted as positive. A water leak test (WLT) was performed on used condoms to verify their integrity. RESULTS: There were total 162 laryngoscopes studied with 83 (51.2%) scopes in the study group and 79 (48.8%) in the control group. Rate of positive bacterial culture were 13.3% and 88.6% in the study and control group, respectively. Although WLT (+) rate of 41% was found in the study group, a high negative culture rate (71.6%) was also noted among the WLT (+) group. CONCLUSIONS: Condom when using as a blade cover during laryngoscopy is a simple, inexpansive and effective way in reducing cross contamination among patients.


Subject(s)
Condoms , Cross Infection/prevention & control , Equipment Contamination/prevention & control , Intubation, Intratracheal/instrumentation , Laryngoscopes/microbiology , Laryngoscopy/methods , Bacteriological Techniques/methods , Condoms/microbiology , Cross Infection/transmission , Emergency Medical Services/methods , Equipment Failure , Humans , Laryngoscopy/standards , Occult Blood , Operating Rooms/methods
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