Protective role of curcumin against lipopolysaccharide-induced inflammation and apoptosis in human neutrophil.

BACKGROUND: Sepsis, an uncontrolled host response to infection, may be life-threatening organ injury. Neutrophils play a critical role in regulation of host immune response to infection. Curcumin, known as a spice and food coloring agent, possesses anti-inflammatory properties. In this study, we investigated the effects of curcumin on lipopolysaccharide (LPS)-induced neutrophil activation with its signaling pathways. METHODS: Isolated human neutrophils were incubated without or with LPS and curcumin, and the expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-8 were assessed by enzyme-linked immunosorbent assays. The expression of mitogen-activated protein kinases such as p38, extracellularsignal-regulated kinase (ERK)1/2, and c-Jun N-terminal kinase (JNK) were evaluated by Western blot analysis. Neutrophil apoptosis was also measured by fluorescence-activated cell sorting (annexin V/propidium iodide) in LPS-stimulated neutrophils under treatment with curcumin. RESULTS: Curcumin attenuated expression of TNF-α, IL-6, and IL-8 and the phosphorylation levels of p38 and JNK, but not ERK1/2, in LPS-stimulated neutrophils. Additionally, curcumin restored the delayed neutrophil apoptosis by LPS-stimulated neutrophils(19.7 ± 3.2 to 38.2 ± 0.5%, P < 0.05). CONCLUSIONS: Our results reveal the underlying mechanism of how curcumin attenuate neutrophil activation and suggest potential clinic applications of curcumin supplementation for patients with severe sepsis and septic shock. Additional clinical studies are required to confirm these in vitro findings.

Effect of BMS-470539 on lipopolysaccharide-induced neutrophil activation.

BACKGROUND: BMS-470539, a recently introduced selective agonist of the melanocortin 1 receptor, is known to have anti-inflammatory properties. In this study, we investigated the effects of BMS-470539 on lipopolysaccharide (LPS)-induced inflammatory responses and delayed apoptosis with its signaling pathways in human neutrophils. METHODS: Isolated human neutrophils were incubated with various concentrations of BMS-470539 (1, 10, and 100 µM) in the presence or absence of LPS (100 ng/ml), and the expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-6, and IL-1ß, were assessed. The effects of BMS-470539 on the expression of mitogen-activated protein kinases (MAPKs), such as p38, extracellular-signal-regulated kinase 1/2, and c-Jun N-terminal kinase, and the expression of nuclear factor kappa B (NF-κB) in LPS-stimulated human neutrophils, were evaluated by enzyme-linked immunosorbent assay. Neutrophil apoptosis was also measured by fluorescence-activated cell sorting (annexin V/propidium iodide) in LPS-stimulated neutrophils under treatment with BMS-470539. RESULTS: BMS-470539 attenuated LPS-induced expression of pro-inflammatory cytokines, and phosphorylation of MAPKs and NF-κB. LPS stimulation reduced neutrophil apoptosis compared to the controls; however, BMS-470539 significantly inhibited the reduction of neutrophil apoptosis. CONCLUSIONS: BMS-470539 can suppress the inflammatory responses of LPS-stimulated neutrophils by inhibition of MAPK pathways or NF-κB pathway, and it can also inhibit LPS-delayed neutrophil apoptosis.

Acute motor weakness of opposite lower extremity after percutaneous epidural neuroplasty.

Recently, percutaneous epidural neuroplasty has become widely used to treat radicular pain caused by spinal stenosis or a herniated intervertebral disc. A 19-year-old female patient suffering from left radicular pain caused by an L4-L5 intervertebral disc herniation underwent percutaneous epidural neuroplasty of the left L5 nerve root using a Racz catheter. After the procedure, the patient complained of acute motor weakness in the right lower leg, on the opposite site to where the neuroplasty was conducted. Emergency surgery was performed, and swelling of the right L5 nerve root was discovered. The patient recovered her motor and sensory functions immediately after the surgery. Theoretically, the injection of a large volume of fluid in a patient with severe spinal stenosis during epidural neuroplasty can increase the pressure on the opposite side of the epidural space, which may cause injury of the opposite nerve by barotrauma from a closed compartment. Practitioners should be aware of this potential complication.

Antiallodynic effect of intrathecal epigallocatechin-3-gallate due to suppression of reactive oxygen species.

BACKGROUND: Green tea modulates neuropathic pain. Reactive oxygen species (ROS) are suggested as a key molecule in the underlying mechanism of neuropathic pain in the spinal cord. We examined the effect of epigallocatechin-3-gallate (EGCG), the major catechin in green tea, in neuropathic pain and clarified the involvement of ROS on the activity of EGCG. METHODS: Neuropathic pain was induced in male Sprague-Dawley rats by spinal nerve ligation (SNL). A polyethylene tube was intrathecally located. Nociceptive degree was estimated by a von Frey filament and expressed as a paw withdrawal threshold (PWT). To determine the role of ROS on the effect of EGCG, a free radical donor (tert-BuOOH) was pretreated before administration of EGCG. ROS activity was assayed by xanthine oxidase (XO) and malondialdehyde (MDA). RESULTS: SNL decreased the PWT compared to sham rats. The decrease remained during the entire observation period. Intrathecal EGCG increased the PWT at the SNL site. Intrathecal tert-BuOOH significantly decreased the effect of EGCG. The levels of both XO and MDA in the spinal cord were increased in SNL rats compared to sham. Intrathecal EGCG decreased the level of XO and MDA. CONCLUSIONS: EGCG may reduce neuropathic pain by SNL due to the suppression of ROS in the spinal cord.

The role of spinal adrenergic receptors on the antinociception of ginsenosides in a rat postoperative pain model.

BACKGROUND: The effect of spinal adrenergic and cholinergic receptors on the anti-nociceptive effect of intrathecal ginsenosides was determined in a rat postoperative pain model. METHODS: Catheters were placed into the intrathecal space of male Sprague-Dawley rats. Postoperative pain was evoked by an incision to the plantar surface of a hind paw. Withdrawal thresholds was used as a nociceptive parameter and was measured with a von Frey filament. After observing the effect of intrathecal ginsenosides, an alpha-1 adrenergic receptor antagonist (prazosin), an alpha-2 adrenergic receptor antagonist (yohimbine), a muscarinic acetylcholine receptor antagonist (atropine), and a nicotinic acetylcholine receptor antagonist (mecamylamine) were given 10 min before administration of the ginsenosides to analyze the contribution of spinal adrenergic and cholinergic receptors on the antinociceptive effect of ginsenosides. RESULTS: Paw incision decreased withdrawal threshold in incised site of paw, but no change of withdrawal threshold was not seen in non-incised site. The intrathecal ginsenosides increased withdrawal threshold of the incised paw in a dose-dependent manner. Pre-treatment with both prazosin and intrathecal yohimbine antagonized the anti-nociceptive effect of the ginsenosides. However, pre-treatments with atropine or mecamylamine had any effect on the antinociceptive activity of ginsenosides. CONCLUSIONS: Intrathecal ginsenosides are effective in attenuation of postoperative pain induced in the rat model. Anti-nociceptive action of ginsenosides is partially mediated by spinal adrenergic receptors, but does not appear to be related to spinal cholinergic receptors.

Additive interaction of intrathecal ginsenosides and neostigmine in the rat formalin test.

BACKGROUND: The authors evaluated the effect of intrathecal mixture of ginsenosides with neostigmine on formalin-induced nociception and made further clear the role of the spinal muscarinic (M) receptors on the activity of ginsenosides. METHODS: A catheter was located in the intrathecal space of male Sprague-Dawley rats. Pain was evoked by injection of formalin solution (5%, 50 µl) to the hindpaw. Isobolographic analysis was done to characterize drug interaction between ginsenosides and neostigmine. The antagonism of ginsenosides-mediated antinociception was determined with M1 receptor antagonist (pirenzepine), M2 receptor antagonist (methoctramine), M3 receptor antagonist (4-DAMP), M4 receptor antagonist (tropicamide). The expression of muscarinic receptor subtypes was examined with RT-PCR. RESULTS: Intrathecal ginsenosides and neostigmine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Isobolographic analysis revealed an additive interaction between ginsenosides and neostigmine in both phases. Intrathecal pirenzepine, methoctramine, 4-DAMP, and tropicamide reversed the antinociception of ginsenosides in both phases. M1-M4 receptors mRNA detected in spinal cord of naïve rats and the injection of formalin decreased the expression of M1 receptor mRNA, but it had no effect on the expression of other three muscarinic receptors mRNA. Intrathecal ginsenosides little affected the expression of all of muscarinic receptors mRNA in formalin-injected rats. CONCLUSIONS: Intrathecal ginsenosides additively interacted with neostigmine in the formalin test. Furthermore, M1-M4 receptors exist in the spinal cord, all of which contribute to the antinocieption of intrathecal ginsenosides.

A comparison between caudal block versus splash block for postoperative analgesia following inguinal herniorrhaphy in children.

BACKGROUND: We wanted to determine the postoperative analgesic efficacy of preincisional caudal epidural block versus instillation (splash block) following inguinal herniorrhaphy in children. METHODS: THIRTY CHILDREN (AGE RANGE: 1-7 years) who were scheduled to undergo inguinal herniorrhaphy were divided into 2 groups: the caudal block group and the splash block group with 15 children in each group. Tracheal intubation was performed. Fifteen children received caudal block with 1.0 ml/kg of 0.25% ropivacaine (Group 1). Caudal block was performed using the loss of resistance method via the sacral hiatus. Fifteen children in Group 2 received local instillation (splash block) in the surgical site with up to 0.4 ml/kg of 0.25% ropivacaine. The patients were observed for 90 minutes in the postanesthesia care unit and then they were transferred to the ward. The pain scores were taken 4 times. We assessed pain using the Faces pain scores. RESULTS: There were no significant differences between the groups regarding the pain scores at 10, 30 and 60 minutes upon entering the postanesthesia care unit. The pain scores of Group 1 were slightly lower at the last evaluation point when compared to that of Group 2. One patient in Group 1 required supplemental postoperative intravenous (IV) tramadol, while all the other patients in both groups did not require supplemental IV tramadol. The intraoperative requirement for sevoflurane was decreased in Group 1 as compared to that of Group 2. There were no major complications related to either type of block. CONCLUSIONS: We conclude that a splash block can have a similar analgesic effect as that of a caudal block for the postoperative herniorrhaphy pain of children.

Roles of adenosine and serotonin receptors on the antinociception of sildenafil in the spinal cord of rats.

PURPOSE: The phosphodiesterase 5 inhibitor sildenafil has antinociceptive effects, mediated by an increase in cGMP. This study examined the role of spinal adenosine and serotonin receptors played in the antinociceptive effects of intrathecal sildenafil. MATERIALS AND METHODS: Intrathecal catheters were inserted into the subarachnoid space of Sprague-Dawley male rats as a drug delivery device. Pain was induced by injecting formalin into the plantar surface of rats and observing nociceptive behavior (flinching response) for 60 minutes. Then, the effects of intrathecal adenosine and serotonin receptor antagonists on the antinociceptive activity of intrathecal sildenafil were examined. RESULTS: Intrathecal sildenafil suppressed the flinching response in a dose-dependent manner during phases 1 and 2 in the formalin test. Both CGS 15943 and dihydroergocristine decreased the antinociceptive effects of sildenafil during phases 1 and 2 in the formalin test. CONCLUSION: Intrathecal sildenafil effectively attenuated the pain evoked by formalin injection. Both adenosine and serotonin receptors may be involved in the antinociceptive action of sildenafil at the spinal level.

Hydrothorax due to extravasation of intravenous contrast through left subclavian catheter -A case report-.

Central venous catheterization is associated with a large number of complications, such as pneumothorax, hydrothorax, hemothorax, phlebothrombosis, pericardial tamponade, air embolism, aberrant placement and line sepsis. There are many case reports of the extravasation of various central venous catheter fluids, including the intravenous fluids, total parenteral nutrition and chemotherapeutic agents into the pleural cavity and mediastinum. These have led to hydrothorax, hydromediastinum and pericardial effusions. We report a case of the extravasation of intravenous contrast into the pleural cavity after dynamic CT through a left subclavian catheter.

Ventricular fibrillation due to coronary spasm at the site of myocardial bridge -A case report-.

Myocardial bridge is a congenital anomaly characterized by narrowing of some of the epicardial coronary arterial segments running in the myocardium during systole. Occasionally, the compression of a coronary artery by a myocardial bridge can be associated with the clinical manifestations of myocardial ischemia, and might even trigger a myocardial infarction or malignant ventricular arrhythmias. We report a case of ventricular fibrillation due to coronary spasm at the site of myocardial bridge. A 56-year-old man who had suffered from bronchial asthma was given remifentanil combined with sevoflurane in general anesthesia for endoscopic sinus surgery. During the surgery, ventricular fibrillation occurred following coronary spasm with bradycardia, hypotension, bronchospasm. we found myocardial bridge that coincided with an area of coronary spasm after coronary angiography.

Very late stent thrombosis of DES implanted patient during noncardiac surgery: A case report.

Very late stent thrombosis after implantation of drug eluting stent is rare, but its consequences are potentially fatal. Stent thrombosis may be occurred in perioperative period because of interruption of anticoagulation therapy and intraoperative hypercoagulability. We report a case of very late stent thrombosis in a 49-year-old male patient during total gastrectomy. ST-segment elevation in lead II occurred during the surgery and followed by cardiac arrest. After external cardiac massage and electrocardioversion, normal sinus rhythm was restored. Postoperative 12 lead ECG showed ST-segment elevation in leads II, III, aVF and serum cardiac enzymes such as CPK, CK-MB, and Troponin T were markedly elevated. Postoperative coronary angiography showed complete occlusion of the right coronary artery stent. Emergency percutaneous transluminal coronary angioplasty was performed and the patient recovered uneventfully.