Anti-Proliferative Effect of Naringenin through p38-Dependent Downregulation of Cyclin D1 in Human Colorectal Cancer Cells

Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells.

Therapy of Pulmonary Thromboembolism under Emergency Byspass System during Anterior Cruciate Ligament Repair: A case report / 대한마취과학회지

A 56 year old female patient was transferred to the operating room for the repair of anterior cruciate ligament under general anesthesia. Initial vital sign was stable, but there was gradual decreases of the blood pressure and end-tidal CO2 after femur tourniquet application. We suspected the pulmonary thromboembolism, and started massive treatment of using ventilator with 100% O2, various invasive monitors and many vasopressors. Because the patient's vital sign was so unstable, we finally made a decision of using emergency bypass system (Capiox EBS(R), Terumo, Japan) by femoral artery and vein. After that, we transferred the patient to intensive care unit, and continued vigorous treatment. The patient was diagnosed as pulmonary thromboembolism by CT scan. We treated her with infusion of heparin and maintained ACT above 200 second. The 4th day at the intensive care unit, we removed the emergency bypass system. We transferred her to general ward without any complication after 12th day postoperatively.

Management of Complete Tracheal Disruption after a Fall

A complete tracheal rupture due to blunt trauma is rare, and a high proportion of patients with this injury die prior to arrival at medical centers. Early diagnosis and prompt management is essential in order to reduce morbidity and mortality. A 38-year-old woman visited the emergency department after a fall from the 4th floor of a building. We confirmed that a complete tracheal disruption 4 cm above the carina by chest CT. We could not insert an endotracheal tube because the distal stump of the trachea was separated by 4 cm from the proximal stump, so we used percutaneous cardiopulmonary bypass for the prevention of hypoxia during the initial operative procedures. We performed resections and reconstruction of the injured trachea. Fourteen days after the operation we confirmed normal healing of the trachea with bronchoscopy. One year after the operation, the patient is healthy with no tracheal problems.

The Effect of Intrathecal Bupivacaine with Hypothermia on Neuronal Protection against Transient Spinal Cord Ischemia in Rats / 대한마취과학회지

BACKGROUND: Local anesthetics can reduece excitotoxic neuronal injury from ischemia. We investigated neuroprotective effects of intrathecally administered bupivacaine and hypothermia in rat model of transient spinal cord ischemia. METHODS: A PE-10 intrathecal catheter was implanted into thirty six male Sprague-Dawley rats through L4-5 interlaminar space. Animals of normothermia (N) and hypothermia (H) groups were administered 15microliter of normal saline, and 15microliter of 0.5% bupivacaine for bupivacaine (B) and bupivacaine-hypothermia (BH) groups. Transient spinal cord ischemia was induced by inflation of a 2 F Fogarty catheter placed into aortic arch for 12 minutes. During ischemia, rectal temperature was maintained to 37.0+/-0.5 degrees C for N and B groups, 34.5 +/- 0.5degrees C for H and BH groups. Motor and sensory deficit score were assessed 2 and 24 hour after reperfusion. Lumbar spinal cords were harvested for histopathology, and for immunoreactivity of heat shock protein 70 (HSP70). RESULTS: The motor and sensory deficit score of N and B group was significantly higher than H group (P < 0.05) and BH group (P < 0.05). There were also significant difference in the motor and sensory deficit score between H and BH group at 24 hr (P < 0.05). Neuronal cell death and immunoreactivity of HSP70 was frequently observed in the N and B groups, but not in the H and BH groups. CONCLUSIONS: These results suggest that intrathecal bupivacaine did not provide neuroprotection during normothermic transient spinal cord ischemia in rats, but it can enhance neuroprotective effects of hypothermia.

Anesthetic Management for Clipping a Intracranial Giant Aneurysm with Low-flow Deep Hypothermic Cardiopulmonary Bypass and Propofol Infusion: A case report / 대한마취과학회지

A 35-year-old male patient underwent surgery to clip a giant middle cerebral artery aneurysm with closed-chest cardiopulmonary bypass using femorofemoral bypass. Deep hypothermia (18-20 degrees C), low-flow cardiopulmonary bypass and propofol infusion (6-8 mg/kg/h) were used under general anesthesia. Venous drainage via femoral vein was suffcient and ventricular distension was not observed on transesophageal echocardiography. On Electroencephalogram, burst suppression pattern was presented due to deep hypothermia and propofol infusion. Instead of deep hypothermic circulatory arrest perfusion flow was maintained at low-flow (33 ml/kg/min) during aneurysmal clipping. Postoperatively, the patient was transferred to intensive care unit and discharged without neurological deficit.

Endoscopic Removal of a Spoon from the Stomach Using Guidewire / 대한소화기내시경학회지

Foreign body ingestion is a relatively uncommon, but potentially serious condition. Most of gastrointestinal foreign bodies pass spontaneously. But, large objectives are usually lodged in the stomach and cause perforation, bleeding, and obstruction. Therefore, prompt retrieval of lodged foreign bodies are necessary before complications develop. Particularly, in the case of long metallic spoon, there have been no cases of spontaneous passage reported. Therefore, prompt retrieval of a metallic spoon are necessary. A 28-year-old woman with schizophrenia who ingested a long spoon for suicidal attempt was referred to our hospital. Simple abdomen showed a 18 cm sized long, metallic spoon with saw-toothed end placed in the stomach. We removed a spoon by an endoscopic technique and an extraction maneuver using a guidewire and a Magill forceps.

A Case of Pulmonary Thromboembolism during Ceaserian Section of Placenta Previa Totalis: A case report / 대한마취과학회지

The pulmonary thromboembolism (PTE) developes occasionally in trauma, surgery and pregnancy. It presents dyspnea, tachycardia, syncope, hypotension and may be fatal by right heart failure. Severe intraoperative PTE is rare. But an intraoperative PTE occurs, it is difficult to diagnose with classic diagnostic measures such as ventilation-perfusion scan, pulmonary angiography, so appropriate management may be delayed. We experienced a case of severe PTE during Ceaserian section of placenta previa totalis. The patient survived and showed complete resolution after 1-year follw-up.

Ambulatory Anesthetic Care for Electroconvulsive Therapy (ECT) in Psychiatric Patients / 대한마취과학회지

We experienced two cases of electroconvulsive therapy (ECT) through ambulatory surgery units. In case 1 patient was a 17 year old male with depressive disorder and the case 2 patient was a 64 year old male also with depressive disorder. A trial of various antidepressants had proved ineffective. They were treated with six ECTs for each case. The case 1 patient complained two times of myalgia suspected to be due to the adverse effects of succinylcholine administration and the case 2 patient showed tachycardia and hypertension due to sympathetic stimulation after application of the current, but the two cases were successfully cared for by ambulatory surgery unit and discharged without severe complications. Perioperative care for individuals who undergo outpatient ECT is similar to the care provided for scheduled ambulatory surgery. Successful performance of ambulatory ECT requires collaboration by psychiatrists, anesthesia care providers, skilled perioperative nurses, affected individuals, and family members.

The Relation between Tourniquet Hypertension and Bispectral Index in Patients Undergoing a Total Knee Arthroplasty / 대한마취과학회지

BACKGROUND: Tourniquet hypertension (TH) may develop from an autonomic reflex consequent to the sensitization of the central nervous system (CNS) due to ischemia of the affected limb and noxious surgical stimulation. TH could be preventable when anesthetic depth is sufficient enough to block plastic changes of the CNS during an operation. This study was aimed to evaluate the efficacy of the bispectral index (BIS) to predict development of TH by assessing correlations between BIS changes and hemodynamic changes during the skin incision. METHODS: Sixty patients who had undergone a total knee arthroplasty with a pneumatic tourniquet during isoflurane anesthesia were selected, and the samples were randomly divided into two groups: BIS 30 (30 - 39) and BIS 40 (40 - 49). Several variables such as BIS, mean arterial pressure (MAP), heart rate (HR) and end tidal concentraion of isoflurane were monitored during the operation. TH was defined as more than a 30% increase in MAP compared with the baseline values during the skin incision. The correlation between BIS changes and MAP and HR changes, and the incidence of TH between BIS groups were compared. RESULTS: The MAP and HR were meaningfully increased in both the BIS 30 and the BIS 40 groups (P < 0.05), but no significant correlations were found between the BIS changes and the MAP and HR changes during the skin incision. The incidence of intraoperative hypertension was not different between the BIS groups. The BIS of the patients who had TH was not different from those who did not have TH. CONCLUSIONS: BIS may not reflect the changes of the CNS and autonomic nervous system induced by noxious surgical stimulation during an operation, and BIS changes during a skin incision cannot be a predictor of TH.

Responses of the Nociceptive Axons to the Inflammatory Mediators and Tumor Necrosis Factor-alpha / 대한마취과학회지

BACKGROUND: Following musculoskeletal injuries, axons are exposed to tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators. Exposure of axons to TNF-alpha and complete Freund's adjuvant (CFA) can cause hyperalgesia or allodynia in the distribution of the affected axons. The hypothesis that TNF-alpha, inflammatory mediators, and inflammation secondary to CFA activate nociceptor axons was tested using teased fiber techniques in the rat. METHODS: Electrophysiologic recordings were made from single nociceptors innervating both deep and cutaneous receptive fields (RF) supplied by the sciatic nerve. The axons proximal to the RF were exposed to either TNF-alpha, a mixture of inflammatory mediators (histamine, serotonin, bradykinin, and prostaglandin), or CFA. RESULTS: In a minority of nociceptors (15%), TNF-alpha rapidly evoked a response that was dose- dependent and transient. There was no difference between deep and cutaneous nociceptors in the incidence of TNF-alpha responses. The majority of neurons responded to TNF-alpha injected into their RFs. No neurons responded to axonal application of either the mixed inflammatory mediators or CFA. CONCLUSIONS: Our data supports that TNF-alpha can induce ectopic electrogenesis in nociceptor axons that innervate both deep and cutaneous tissues. This activity may correlate to the human perception of radicular pain that is often associated with neuritis.

Effect of the K+ Channel Modulations on Glutamate and K+ Concentrations in Rabbit Hippocampus during Transient Global Ischemia / 대한마취과학회지

BACKGROUND: Cerebral ischemia causes an increase in extracellular potassium ([K+]e) through activation of the KATP channel. This increase in [K+]e could result in neuronal depolarization and a reversal of the glutamate uptake system in glia. This may further contribute to the excessive concentrations of glutamate and asparate in the extracellular space during ischemia. If the early rise in [K+]e during ischemia could be attenuated, less excitotoxic neuronal damage may be the result. However, activation of KATP channels has been shown to attenuate the anoxia induced depolarization in the hippocampus and may reduce the release of excitatory neurotransmitters during cerebral ischemia. In this study, we address the question of whether KATP channel modulation affects [K+]e and whether it is related with extracellular glutamate concentrations. METHODS: After approval by the Animal Care and Use Committee, 18 New Zealand white rabbits were anesthetized with halothane and mechanically ventilated to maintain normocarbia. Microdialysis catheters were inserted into the left dorsal hippocampus and perfused with artificial cerebrospinal fluid at 2 ml/min. K+ sensitive microelectrodes were inserted into the contralateral hippocampus. A pneumatic tourniquet was placed loosely around the neck. Animals were randomized to receive glibenclamide (n=5, KATP blocker, 3.7 mg/kg) or cromakalim (n=5, KATP opener, 0.5 mg/kg). The control group (n=6) had neither drug. Ten-minute period of global cerebral ischemia was produced by inflation of the tourniquet combined with induced hypotension. Hippocampal [K+]e was measured throughout the periischemic period and glutamate concentrations in dialysate were determined by high-performance liquid chromatography. Peak levels were compared by ANOVA. RESULTS: Glutamate concentration significantly increased during ischemia period for all groups (p<0.05). In glibenclamide treated animals, brain glutamate concentration increased markedly during early reperfusion (t=I+15) compared to other groups (p<0.05). There were no statistical differences on ischemia-induced increases in [K+]e among the three groups. CONCLUSIONS: Although it was not possible to demonstrate an effect of modulators of the ATP sensitive K+ channel on [K+]e, glibenclamide increased glutamate during reperfusion. This paradoxical increase in glutamate after administration of a K+ channel blocker suggests that the mechanism of glutamate release is not related to [K+]e change.

Response to Capsaicin and Changes in Sodium Currents in Dorsal Root Ganglion Neurons of Neuropathic Rats / 대한마취과학회지

BACKGROUND: Allodynia, one of the most debilitating symptoms of neuropathic pain syndromes, can be defined as `pain due to a stimulus that does not normally provoke pain'. Subsets of dorsal root ganglion (DRG) neurons involved in nociception are characteristically expressed capsaicin sensitivity and high proportion of tetrodotoxin resistant sodium current (TTX-R INa). We performed an experiment to elucidate whether nerve injury induced mechanical allodynia could be resulted from elctrophysiological modulation of large, nonnociceptive afferent neurons to nociceptors. METHODS: Whole cell patch clamp recordings were made from acutely dissociated dorsal root ganglion (DRG) neurons of normal and experimental neuropathic rats. We compared the proportion of capsaicin sensitive neurons which responded to capsaicin (1micrometer) with an inward current > or = 100 pA in amplitude and the proportion of sodium channel subtypes measured in the absence and presence of tetrodotoxin (1micrometer), in small and large DRG neurons. RESULTS: The proportion of capsaicin sensitive cells to total number of cells tested was not changed by nerve injury in both small and large cell populations. In large cell population of nerve injured rats, the proportion of TTX-R INa was significantly increased as compared with normal group (p <0.05), and in small cell population of nerve injured rats, TTX-S INa was increased, but there was no statistical significance. CONCLUSIONS: These data indicate that expression of the sensitivity to capsaicin in DRG neurons would not be altered by nerve injury and increased TTX-R INa in large cell population of nerve injured DRG may underlie increased excitability.