OBJECTIVE: : To determine the effects of cysteinyl leukotriene receptors (CysLTR and CysLTR) on phagocytosis of mouse BV2 microglial cells. METHODS: : BV2 cells were stimulated with microglial activators lipopolysaccharide (LPS) or CysLT receptor agonists LTD. The phagocytosis of BV2 cells was observed by immunofluorescence analysis and flow cytometry. The intracellular distributions of CysLTR and CysLTR in BV2 cells were examined with immunofluorescence staining. RESULTS: : Both LPS and LTD could significantly enhance the phagocytosis of BV2 cells, and such effect could be inhibited by CysLTR selective antagonist Montelukast and CysLTR selective antagonist HAMI 3379. The activation of BV2 cells induced by LTD or LPS resulted in changes in intracellular distributions of CysLTR and CysLTR. CysLTR and CysLTR was co-localization with a similar distribution. CONCLUSIONS : CysLTR and CysLTR regulate the phagocytosis of mouse BV2 microglial cells with a synergistic effect.
Acetates ; pharmacology ; Animals ; Cell Line ; Cyclohexanecarboxylic Acids ; pharmacology ; Lipopolysaccharides ; pharmacology ; Mice ; Microglia ; cytology ; Phagocytosis ; drug effects ; Phthalic Acids ; pharmacology ; Protein Binding ; drug effects ; Quinolines ; pharmacology ; Receptors, Leukotriene ; agonists ; metabolism

BACKGROUND: Although both pregabalin and gabapentin are known to be useful for treating lumbar radiating pain and reducing the incidence of surgery, the oral corticosteroids sometimes offer a dramatic effect on severe radiating pain despite the lack of scientific evidence. METHODS: A total of 54 patients were enrolled among 703 patients who complained of lumbar radiating pain. Twenty patients who received an oral corticosteroid was classified as group A and 20 patients who received the control drugs (pregabalin or gabapentin) as group B. Oswestry Disability Index (ODI), Revised Roland Morris disability questionnaire (RMDQ), Short Form 36 (SF-36) questionnaire, lumbar radiating pain, objective patient satisfaction, and objective improvement of patients or physicians were assessed at 2, 6, and 12 weeks after medication. RESULTS: No difference in the sex ratio and age was observed between the groups (p = 0.70 and p = 0.13, respectively). Group A showed greater improvement in radiating pain after 2, 6, and 12 weeks than group B (p < 0.001, p = 0.001, and p < 0.001, respectively). No differences were observed between the groups in satisfaction at the beginning and 12 weeks after taking the medication (p = 0.062 and p = 0.061, respectively) and in objective improvement of patients and physicians (p = 0.657 and p = 0.748, respectively). Group A was less disabled and had greater physical health scores than group B (p = 0.014 and p = 0.017, respectively). CONCLUSIONS: Oral corticosteroids for the treatment of lumbar radiating pain can be more effective in pain relief than gabapentin or pregabalin. The satisfaction of patients and physicians with the drug and objective improvement status were not inferior to that with gabapentin or pregabalin.
Adolescent ; Adrenal Cortex Hormones/*therapeutic use ; Adult ; Aged ; Amines/therapeutic use ; Analgesics/therapeutic use ; Cyclohexanecarboxylic Acids/therapeutic use ; Female ; Humans ; Low Back Pain/*drug therapy/*physiopathology ; Lumbosacral Region/physiopathology ; Male ; Middle Aged ; Patient Satisfaction/statistics & numerical data ; Pregabalin/therapeutic use ; Quality of Life ; Radiculopathy/drug therapy ; Surveys and Questionnaires ; Young Adult ; gamma-Aminobutyric Acid/therapeutic use

This study aims to detect the expression of metabotropic glutamate receptors (mGluRs) in lung carcinoma A549 cells, and to investigate the effects of mGluR8 and mGluR4 activation on the growth of A549 cells in vitro. The mRNA expression levels of the 8 subtypes of mGluRs in A549 cells were determined by real-time PCR. Immunohistochemistry was used to analyze the protein expression of mGluR4 and mGluR8 in A549 cells and lung tissue sections obtained from lung adenocarcinoma patients. To observe the effects of mGluR8 and mGluR4 activation on the growth of A549 cells, the cultured cells were treated with (S)-3,4-DCPG (an agonist of mGluR8) and VU0155041 (an agonist of mGluR4), respectively, and then the cell viability was analyzed by CCK-8 kit, the percentage of DNA synthesis was detected by EdU incorporation, and the apoptosis of the cells was measured by hoechst 33258 staining and flow cytometry. The results showed that there were low expressions of mGluR1, mGluR5, mGluR6, mGluR7 mRNA, no expression of mGluR2 and mGluR3 mRNA, and high expressions of mGluR8 and mGluR4 mRNA in A549 cells. Accordingly, there were also mGluR4 and mGluR8 protein expressions in the A549 cells and the lung adenocarcinoma tissue sections. VU0155041 had no effect on the growth of A549 cells, but (S)-3,4-DCPG significantly decreased the cells' growth in a dose-dependent manner and increased the apoptosis of the cells. The results revealed a role of mGluR8 in the growth and apoptosis of A549 cells and suggested a potential target for clinical treatment of lung cancer.
Anilides ; pharmacology ; Apoptosis ; Benzoates ; pharmacology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Cyclohexanecarboxylic Acids ; pharmacology ; Glycine ; analogs & derivatives ; pharmacology ; Humans ; Lung Neoplasms ; pathology ; Receptors, Metabotropic Glutamate ; physiology

OBJECTIVETo study the clinical effects of gabapentin on the treatment of pruritus of scar resulting from deep partial-thickness burn.

METHODSA total of fifty-eight patients suffering from pruritus of scar after deep partial-thickness burn were hospitalized from January 2013 to January 2014. Patients were divided into placebo group (n =18, treated with oral vitamin C in the dose of 100 mg for 4 weeks, twice per day) , cetirizine group (n = 20, treated with oral cetirizine in the dose of 10 mg for 4 weeks, twice per day) , and gabapentin group (n = 20, treated with oral gabapentin in the dose of 300 mg for 4 weeks, twice per day) . Before treatment and on post treatment day (PTD) 3 and 28, the Visual Analog Scale (VAS) was used to assess the itching degree, and the mean scores were recorded. The remission rates of pruritus on PTD 3 and 28 were calculated. The adverse effects were observed during treatment. Data were processed with analysis of variance, q test, and chi-square test.

RESULTSCompared with that before treatment, the itching degree of patients with light, moderate, and severe itching in placebo group was not relieved after treatment; the itching degree of patients with moderate or severe itching in cetirizine group was alleviated after treatment, but not in patients with light itching; itching degree of all patients in gabapentin group was significantly relieved after treatment. There were no obvious differences in VAS scores among the 3 groups before treatment (F = 2.78, P > 0.05). On PTD 3 and 28, the VAS scores of patients in both gabapentin group [(2.3 ± 0.8) and (0.6 ± 0.3) points] and cetirizine group [(4.2 ± 1.7) and (2.8 ± 1.2) points] were lower than those in placebo group [(5.7 ± 2.0) and (5.7 ± 1.9) points, with q values from 6.70 to 7.75, P values below 0.05]. The VAS scores of patients in gabapentin group on PTD 3 and 28 were lower than those in cetirizine group (with q values respectively 6.30 and 6.90, P values below 0.05). The remission rates of pruritus of patients in gabapentin group on PTD 3 and 28 were respectively (66 ± 20)% and (91 ± 17)%, and they were higher than those in cetirizine group [(33 ± 8)% and (56 ± 14)%, with q values respectively 4.70 and 3.82, P values below 0.05]. The remission rate of pruritus of patients in placebo group on PTD 3 and 28 was 0, which was lower than that of the other 2 groups each (with q values from 3.94 to 6.76, P values below 0.05). During the course of treatment, 5 patients in gabapentin group suffered from adverse effects including mild-to-moderate drowsiness and dizziness, but they disappeared one week later. No adverse effects were observed in patients of the other two groups.

CONCLUSIONSFor patients with deep partial-thickness burn, gabapentin can effectively alleviate scar itching after wound healing with safety.

Amines ; administration & dosage ; therapeutic use ; Analgesics ; therapeutic use ; Ascorbic Acid ; administration & dosage ; Burns ; complications ; Cetirizine ; administration & dosage ; Cicatrix ; Cyclohexanecarboxylic Acids ; administration & dosage ; therapeutic use ; Humans ; Pruritus ; drug therapy ; Skin Transplantation ; Treatment Outcome ; Visual Analog Scale ; Wound Healing ; gamma-Aminobutyric Acid ; administration & dosage ; therapeutic use

OBJECTIVETo investigate the antioxidative effects of two cysteinyl leukotriene receptors antagonists (CysLT1R and CysLT2R) montelukast and HAMI 3379 on ischemic injury of rat cortical neurons in vitro.

METHODSCultured rat cortical neurons were pretreated with CysLT1R antagonist montelukast and CysLT2R antagonist HAMI 3379, and then exposed to oxygen-glucose deprivation/recovery (OGD/R）or H2O2. Reactive oxygen species (ROS) mitochondrial membrane potential (MMP) depolarization, neuronal viability and lactate dehydrogenase (LDH) release were determined. Meanwhile, RNA interference was used to inhibit the expression of CysLT1R and CysLT2R，and the effects were observed.

RESULTSROS production in neurons was significantly increased after 1 h OGD, which reached the peak at 30 min and lasted for 1.5 h after recovery. Montelukast and HAMI 3379 at 0.01-1μmol/L moderately decreased OGD/R-induced ROS production (P<0.05). Montelukast mildly attenuated OGD/R-induced MMP depolarization (P<0.05)，but HAMI 3379 had no effect. H2O2 reduced neuronal viability and increased LDH release, namely inducing neuronal injury. Montelukast and HAMI 3379 at 0.1-1μmol/L moderately attenuated H2O2-induced neuronal injury (P<0.05). However, both CysLT1R siRNA and CysLT2R shRNA did not significantly affect the responses mentioned above.

CONCLUSIONIn ischemic neuronal injury, montelukast and HAMI 3379 exert a moderate antioxidative effect, and this effect may be receptor-independent.

Acetates ; pharmacology ; Animals ; Antioxidants ; pharmacology ; Cell Hypoxia ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Cerebral Cortex ; cytology ; Cyclohexanecarboxylic Acids ; pharmacology ; Leukotriene Antagonists ; pharmacology ; Neurons ; drug effects ; metabolism ; Phthalic Acids ; pharmacology ; Quinolines ; pharmacology ; Rats ; Reactive Oxygen Species ; metabolism

We examined the possible anti-inflammatory mechanisms of gabapentin in the attenuation of neuropathic pain and the interaction between the anti-allodynic effects of gabapentin and interleukin-10 (IL-10) expression in a rat model of neuropathic pain. The anti-allodynic effect of intrathecal gabapentin was examined over a 7-day period. The anti-allodynic effects of IL-10 was measured, and the effects of anti-IL-10 antibody on the gabapentin were assessed. On day 7, the concentrations of pro-inflammatory cytokines and IL-10 were measured. Gabapentin produced an anti-allodynic effect over the 7-day period, reducing the expression of pro-inflammatory cytokines but increasing the expression of IL-10 (TNF-alpha, 316.0 +/- 69.7 pg/mL vs 88.8 +/- 24.4 pg/mL; IL-1beta, 1,212.9 +/- 104.5 vs 577.4 +/- 97.1 pg/mL; IL-6, 254.0 +/- 64.8 pg/mL vs 125.5 +/- 44.1 pg/mL; IL-10, 532.1 +/- 78.7 pg/mL vs 918.9 +/- 63.1 pg/mL). The suppressive effect of gabapentin on pro-inflammatory cytokine expression was partially blocked by the anti-IL-10 antibody. Expression of pro-inflammatory cytokines was significantly attenuated by daily injections of IL-10. The anti-allodynic effects of gabapentin may be caused by upregulation of IL-10 expression in the spinal cord, which leads to inhibition of the expression of pro-inflammatory cytokines in the spinal cords.
Amines/pharmacology/*therapeutic use ; Analgesics/pharmacology/*therapeutic use ; Animals ; Antibodies/immunology/pharmacology ; Behavior, Animal/drug effects ; Cyclohexanecarboxylic Acids/pharmacology/*therapeutic use ; Cytokines/*metabolism ; Disease Models, Animal ; Injections, Spinal ; Interleukin-10/genetics/immunology/*metabolism ; Male ; Neuralgia/*drug therapy/metabolism/pathology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/biosynthesis/genetics/pharmacology ; Spinal Cord/metabolism ; Up-Regulation ; gamma-Aminobutyric Acid/pharmacology/*therapeutic use

Restless legs syndrome (RLS) is a sensorimotor neurologic disorder, in which the primary symptom is a compelling urge to move the legs accompanied by unpleasant and disturbing sensations in the legs. RLS is relatively common, affecting 2.5 to 15% of the general population, with prevalence rates increasing alongside age. Sleep disturbance is the most common symptom owing to RLS leg symptoms. In addition, daytime dysfunction, cognitive decline, and mood disturbance are also common in patients with RLS. Iron and dopamine are implicated in the pathophysiology of RLS, however, the underlying pathophysiology of RLS is still not fully understood. The diagnosis can be made based on the symptom characteristics, differential diagnosis is important because many conditions could mimic RLS symptoms. Dopaminergic agents are recommended for the first line treatment of RLS. Alpha2delta anticonvulsants such as gabapentin and pregabalin are also effective for controlling RLS symptoms.
Amines ; Anticonvulsants ; Cyclohexanecarboxylic Acids ; Diagnosis* ; Diagnosis, Differential ; Dopamine ; Dopamine Agents ; Dyssomnias ; gamma-Aminobutyric Acid ; Humans ; Iron ; Leg ; Nervous System Diseases ; Prevalence ; Restless Legs Syndrome* ; Sensation ; Pregabalin

PURPOSE: Patients with bladder pain syndrome/interstitial cystitis (BPS/IC) can have pain as a main symptom and overactive bladder (OAB) symptoms that are directly or indirectly related to a major mechanism that causes pain. The primary purpose of this study is firstly to identify the prevalence rate of OAB symptoms in patients with BPS/IC, secondly to identify changes in OAB symptoms after low-dose triple therapy, and thirdly to build a theoretical foundation to improve quality of life for patients. METHODS: Patients who met the inclusion criteria of BPS/IC through basic tests including the O'Leary-Sant symptom index, overactive bladder symptom score (OABSS), and visual analog scale (VAS) were identified. Treatment-based changes in OAB symptoms were identified using the IC Symptom Index and IC Problem Index (ICSI/ICPI), OABSS, and VAS before, and 4 and 12 weeks after low-dose triple therapy. RESULTS: The patients consisted of 3 men and 20 women, and their mean age was 61.9 years (41.0-83.2 years). Comparing values before treatment, and 4 and 12 weeks after treatment (baseline vs. 4 weeks to baseline vs. 12 weeks), the rates of improvement were as follows: ICSI, 44.2% to 63.7%; ICPI, 46.9% to 59.4%; OABSS, 34.3% to 58.2%; and VAS, 53.6% to 75.0%, which showed statistically significant differences (P<0.05). However, comparing values at 4 and 12 weeks after treatment (4 weeks vs. 12 weeks), the ICSI and VAS showed a statistically significant decrease (P<0.05). The ICPI and OABSS showed slight improvement, but no statistically significant differences (P>0.05). CONCLUSIONS: Low-dose triple therapy in BPS/IC results in a clear decrease in OAB symptoms in the first 4 weeks after treatment, and additional treatment for 8 weeks had a partial effect with varied statistical significances depending on the questionnaires.
Amines ; Amitriptyline ; Cyclohexanecarboxylic Acids ; Cystitis ; Cystitis, Interstitial ; Female ; gamma-Aminobutyric Acid ; Humans ; Male ; Prevalence ; Quality of Life ; Sperm Injections, Intracytoplasmic ; Urinary Bladder ; Urinary Bladder, Overactive

OBJECTIVETo investigate the effects of CysLT receptor agonist leukotriene D4(LTD4) and antagonists on activation of microglia BV2 cells.

METHODSThe expression of CysLT1 and CysLT2 protein was determined by Western blotting and immunostaining in microglia BV2 cells. BV2 cells were pretreated with or without CysLT1 receptor selective antagonist montelukast, CysLT2 receptor selective antagonist HAMI 3379, or CysLT1/CysLT2 receptor dual antagonist BAY u9773 for 30 min, then the cells were treated with LTD4 for 24 h. Cell viability was detected by MTT reduction assay. Phagocytosis and mRNA expression of IL-6 were determined by fluorescent bead tracking and RT-PCR, respectively.

RESULTSIn BV2 cells, LTD4 did not affect proliferation but significantly enhanced phagocytosis and increased IL-6 mRNA expression in a concentration-dependent manner. LTD4 at 100 nmol/L induced a 1.4-fold increase of phagocytic index and a 2-fold up-regulation of IL-6 mRNA expression (P<0.01). HAMI 3379 and BAY u9773 (100 nmol/L) further increased LTD4-induced phagocytosis; BAY u9773 and montelukast decreased LTD4-induced IL-6 mRNA expression, while HAMI 3379 had no effect on that.

CONCLUSIONLTD4 activates BV2 cells in vitro and enhances IL-6 mRNA expression mediated by CysLT1 receptor, LTD4 induces phagocytosis which might be negatively regulated by CysLT2 receptor in BV2 cells.

Acetates ; pharmacology ; Cell Line ; Cell Proliferation ; Cyclohexanecarboxylic Acids ; pharmacology ; Humans ; Interleukin-6 ; metabolism ; Leukotriene Antagonists ; pharmacology ; Leukotriene D4 ; pharmacology ; Microglia ; cytology ; metabolism ; Phagocytosis ; Phthalic Acids ; pharmacology ; Quinolines ; pharmacology ; Receptors, Leukotriene ; metabolism ; SRS-A ; analogs & derivatives ; pharmacology

BACKGROUND: Postoperative sore throat (POST) is considered a usual complication after tracheal intubation, especially, thyroid surgery. Gabapentin is a widely studied multimodal perioperative drug, which can be used to treat acute postoperative pain. The primary endpoints of this study was a reduction of the incidence of POST at rest and during the swallowing movements after thyroid surgery. And the second endpoints was a reduction of the intensity of the POST after thyroid surgery. METHODS: Seventy-one patients that underwent elective thyroid surgery received either gabapentin (Neurontin(TM) 600 mg) or placebo, orally, one hour before anesthesia. The VAS scores and incidences of POST and adverse effects were determined at 1 hr, 6 hr, 12 hr, and 24 hr after surgery at rest and during swallowing movement. RESULTS: The gabapentin group (N = 36) showed a lower incidence of POST than the placebo group (N = 35) (47% vs. 78%, P = 0.038), and had significant lower VAS score at 6 and 24 hours after surgery in the resting state. However, during the movement, no intergroup differences were found in terms of the incidence of POST (83% vs. 91%, P = 0.305) or VAS score. Furthermore, no significant difference was observed between the two groups, in adverse effects. CONCLUSIONS: Gabapentin (Neurontin(TM) 600 mg) administered 1 hr before anesthesia reduced the intensity and incidence of POST during the resting state without a significant adverse event, during the 24 hr after thyroid surgery. However, gabapentin did not reduce the intensity and incidence of POST during the swallowing movement.
Amines ; Anesthesia ; Cyclohexanecarboxylic Acids ; Deglutition ; gamma-Aminobutyric Acid ; Humans ; Incidence ; Intubation ; Pain, Postoperative ; Pharyngitis ; Thyroid Gland ; Thyroid Neoplasms