Here we have investigated how lactosylceramide (LacCer) modulates gene expression of adhesion molecules in TNF-alpha and IFNgamma (CM)-stimulated astrocytes. We have observed that stimulation of astrocytes with CM increased the gene expression of ICAM-1 and VCAM-1. D-Threo-1-phenyl- 2-decanoylamino-3-morpholino-1-propanol (PDMP) and N-butyldeoxynojirimycin (NBDNJ), inhibitors of glucosylceramide synthase (GLS) and LacCer synthase (galactosyltransferase, GalT-2), inhibited the gene expression of ICAM-1 and VCAM-1 and activation of their gene promoter induced by CM, which were reversed by exogenously supplied LacCer. Silencing of GalT-2 gene using its antisense oligonucleotides also attenuated CM-induced ICAM-1 and VCAM-1 expression, which were reversed by LacCer. PDMP treatment and silencing of GalT-2 gene significantly reduced CM-induced luciferase activities in NF-KB, AP-1, GAS, and STAT-3 luciferase vectors-transfected cells. In addition, LacCer reversed the inhibition of NF-KB and STAT-1 luciferase activities by PDMP. Taken together, our results suggest that LacCer may play a crucial role in the expression of ICAM-1 and VCAM-1 via modulating transcription factors, such as NF-KB, AP-1, STAT-1, and STAT-3 in CM-stimulated astrocytes.
1-Deoxynojirimycin ; Antigens, CD ; Astrocytes ; Galactosyltransferases ; Gene Expression ; Glucosyltransferases ; Intercellular Adhesion Molecule-1 ; Lactosylceramides ; Luciferases ; Morpholines ; NF-kappa B ; Oligonucleotides, Antisense ; Transcription Factor AP-1 ; Transcription Factors ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1

PURPOSE: Local anesthetic wound infusion has been previously investigated in postoperative pain management. However, a limited number of studies have evaluated its use in laparoscopic colorectal surgery. This study aims to evaluate whether ropivacaine wound infusion is effective for postoperative pain management after laparoscopic surgery in patients with colorectal cancer. METHODS: This prospective study included 184 patients who underwent laparoscopic surgery for colorectal cancer between July 2012 and June 2013. The patients were grouped as the combined group (intravenous patient-controlled analgesia [IV-PCA] plus continuous wound infusion with ropivacaine, n = 92) and the PCA group (IV-PCA only, n = 92). Efficacy and safety were assessed in terms of numeric rating scale (NRS) pain score, opioid consumption, postoperative recovery, and complications. RESULTS: The total quantity of PCA fentanyl was significantly less in the combined group than in the PCA group (P < 0.001). The NRS score of the combined group was not higher than in the PCA group, despite less opioid consumption. There were no differences between groups for postoperative recovery and most complications, including wound complications. However, the rate of nausea and vomiting was significantly lower in the combined group (P = 0.022). CONCLUSION: Ropivacaine wound infusion significantly reduced postoperative opioid requirements and the rate of nausea/vomiting. This study showed clinical efficacy of ropivacaine wound infusion for postoperative pain control in colorectal cancer patients undergoing laparoscopic surgery.
Analgesia, Patient-Controlled ; Anesthetics, Local ; Colorectal Neoplasms ; Colorectal Surgery* ; Fentanyl ; Humans ; Laparoscopy ; Nausea ; Pain, Postoperative ; Passive Cutaneous Anaphylaxis ; Prospective Studies ; Treatment Outcome ; Vomiting ; Wounds and Injuries*

Opuntia ficus-indica var. saboten. is widely cultivated in Jeju Island (South Korea) for use in manufacture of health foods. This study described antidepressant effect of two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. The expression of the hypothalamic POMC mRNA or plasma beta-endorphin levels were increased by extract of Opintia ficus-indica var. saboten or its flavoniods administered orally. In addition, antidepressant activity was studied using tail suspension test (TST), forced swimming test (FST) and rota-rod test in chronically restraint immobilization stress group in mice. After restraint stress (2 hrs/day for 14 days), animals were kept in cage for 14 days without any further stress, bet with drugs. Mice were fed with a diet supplemented for 14 days and during the behavioral test period with kaempferol or quercitrin (30 mg/kg/day). POMC mRNA or plasma beta-endorphin level was increased by extract of Opintia ficus-indica var. saboten and its flavoniods. In addition, immobility time in TST and FST was significantly reduced by kaempferol or quercitrin. In rota-rod test, the time of permanence was maintained to the semblance of control group in turning at 15 rpm. Our results suggest that two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. show a potent antidepressant effect.
Animals ; beta-Endorphin ; Diet ; Flavonoids ; Hindlimb Suspension ; Immobilization ; Kaempferols ; Mice ; Opuntia ; Plasma ; Pro-Opiomelanocortin ; Quercetin ; RNA, Messenger ; Swimming ; Food, Organic

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome is an uncommon congenital abnormality of the female urogenital tract characterized by the triad of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. A 13-year-old female presented with acute lower abdominal pain. Magnetic resonance imaging (MRI) revealed uterine didelphys, hematometrocolpos, obstructed hemivagina, and right ipsilateral agenesis, consistent with OHVIRA syndrome. Also, a well-defined mass with fluid signal intensity, mimicking adnexal neoplasm was seen in the right lower pelvic cavity adjacent to the posterior wall of the bladder. Vaginal septotomy and drainage of hematometrocolpos were done initially, but unilateral hysterectomy was later performed to relieve the patient's symptoms. The cystic mass in the right lower pelvic cavity was also excised and confirmed as a blind megaureter.
Abdominal Pain ; Adolescent ; Congenital Abnormalities ; Drainage ; Female ; Humans ; Hysterectomy ; Magnetic Resonance Imaging* ; Urinary Bladder

In the present study, the antinociceptive profiles of Agrimonia pilosa Ledeb extract were examined in ICR mice. Agrimonia pilosa Ledeb extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Agrimonia pilosa Ledeb extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 microg) was diminished by Agrimonia pilosa Ledeb extract. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Agrimonia pilosa Ledeb extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Agrimonia pilosa Ledeb extract in the writhing test. Our results suggest that Agrimonia pilosa Ledeb extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Agrimonia pilosa Ledeb extract may be mediated by alpha2-adrenergic receptor, but not opioidergic and serotonergic receptors.
Agrimonia ; Animals ; Methysergide ; Mice ; Mice, Inbred ICR ; Naloxone ; Reaction Time ; Substance P ; Yohimbine

Visnagin (4-methoxy-7-methyl-5H-furo[3,2-g][1]-benzopyran-5-one), which is an active principle extracted from the fruits of Ammi visnaga, has been used as a treatment for low blood-pressure and blocked blood vessel contraction by inhibition of calcium influx into blood cells. However, the neuroprotective effect of visnagin was not clearly known until now. Thus, we investigated whether visnagin has a neuroprotective effect against kainic acid (KA)-induced neuronal cell death. In the cresyl violet staining, pre-treatment or post-treatment visnagin (100 mg/kg, p.o. or i.p.) showed a neuroprotective effect on KA (0.1 microgram) toxicity. KA-induced gliosis and proinflammatory marker (IL-1beta, TNF-alpha, IL-6, and COX-2) inductions were also suppressed by visnagin administration. These results suggest that visnagin has a neuroprotective effect in terms of suppressing KA-induced pathogenesis in the brain, and that these neuroprotective effects are associated with its anti-inflammatory effects.
Ammi ; Animals ; Benzoxazines ; Blood Cells ; Blood Vessels ; Brain ; Calcium ; Cell Death ; Contracts ; Cytokines ; Fruit ; Gliosis ; Glycosaminoglycans ; Hippocampus ; Interleukin-6 ; Kainic Acid ; Khellin ; Mice ; Neurons ; Neuroprotective Agents ; Tumor Necrosis Factor-alpha ; Viola

The present study demonstrates the effect of fibrates, agonists of PPARalpha on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-1beta (10 ng/ml), IFNgamma (10 ng/ml), and TNF-alpha (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and 10 micrometer) reduced the IFNgamma and IL-1beta-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the IFNgamma and IL-1beta-induced cell proliferation, released IL-6 level was measured. IFNgamma and IL-1beta cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the IFNgamma and IL-1beta-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in IFNgamma and IL-1beta-stimulated astrocytes. Taken together, these results clearly suggest that activation of PPARalpha attenuates the IFNgamma and IL-1beta-induced cell proliferation through IL-6 independent pathway.
Astrocytes ; Bezafibrate ; Cell Proliferation ; Cytokines ; Fenofibrate ; Fibric Acids ; Interleukin-6 ; PPAR alpha ; RNA, Messenger ; Tumor Necrosis Factor-alpha

In the present study, the antinociceptive profiles of Campanula punctata extract were examined in ICR mice. The Campanula punctata contain a large dose of saponin. Campanula punctata extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Campanula punctata extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 microgram) was diminished by Campanula punctata extract. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Campanula punctata extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Campanula punctata extract in the writhing test. Our results suggest that Campanula punctata extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Campanula punctata extract may be mediated by alpha2-adrenergic receptor, but not opioidergic and serotonergic receptors.
Animals ; Campanulaceae ; Methysergide ; Mice ; Mice, Inbred ICR ; Naloxone ; Reaction Time ; Saponins ; Substance P ; Yohimbine

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 microg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.
Animals ; Blood Glucose* ; Brain ; Corticosterone ; Glipizide ; Glyburide ; Immobilization* ; Insulin ; Mice ; Mice, Inbred ICR ; Plasma ; Tolazamide

Sepsis is the life-threatening response to infection which can lead to tissue damage, organ failure, and death. In the current study, the effect of orally administered D-glucose on the mortality and the blood glucose level induced by D-Galactosamine (GaLN)/lipopolysaccharide (LPS)-induced sepsis was examined in ICR mice. After various amounts of D-glucose (from 1 to 8 g/kg) were orally fed, sepsis was induced by injecting intraperitoneally (i.p.) the mixture of GaLN /LPS. Oral pre-treatment with D-glucose dose-dependently increased the blood glucose level and caused a reduction of sepsis-induced mortality. The oral post-treatment with D-glucose (8 g/kg) up to 3 h caused an elevation of the blood glucose level and protected the mortality observed in sepsis model. However, D-glucose post-treated at 6, 9, or 12 h after sepsis induction did not affect the mortality and the blood glucose level induced by sepsis. Furthermore, the intrathecal (i.t.) pretreatment once with pertussis toxin (PTX; 0.1 microg/5 ml) for 6 days caused a reduction of D-glucose-induced protection of mortality and hyperglycemia. Furthermore, once the hypoglycemic state is continued up to 6 h after sepsis initiated, sepsis-induced mortality could not be reversed by D-glucose fed orally. Based on these findings, it is assumed that the hypoglycemic duration between 3 and 6 h after the sepsis induction may be a critical time of period for the survival. D-glucose-induced protective effect against sepsis-induced mortality appears to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Finally, the production of hyperglycemic state may be critical for the survival against the sepsis-induced mortality.
Animals ; Blood Glucose ; Glucose* ; GTP-Binding Proteins ; Hyperglycemia ; Mice ; Mice, Inbred ICR ; Mortality* ; Pertussis Toxin ; Sepsis* ; Spinal Cord