Safety of the inter-nipple line hand position landmark for chest compression.

BACKGROUND: No previous study has investigated the safety of hand position during chest compression determined by the inter-nipple line, in which the heel of one hand is positioned on the centre of the chest between the nipples, from the standpoint of prevention of organ injury. METHODS: We measured the distance from the xiphisternal junction to the inter-nipple line (dN) in 1000 surgical patients and the heel length (H) of hands in 100 healthy volunteers, then used the formula H/2-dN to determine the amount of deviation when the heel of the rescuer's hand extended to the xiphoid process (D). Next, 100 surgical patients were randomly assigned to 18 anaesthesiologists, who placed the heels of their hands on the sternum for validation. RESULTS: The D value was positive in 551 patients, indicating that the heel may extend to the xiphoid process during chest compression in those individuals. Multivariate logistic-regression analyses showed that deviations beyond the xiphoid process to the epigastric region were more likely to occur in female (OR 3.52), elderly (OR 2.00), and short-statured (OR 2.09) patients, and with male rescuers (OR 2.81). During actual positioning, deviation occurred in 51 patients and extended to the epigastric region in 5 females. CONCLUSIONS: Simulation of hand position determined by the inter-nipple line resulted in placement of the rescuer's hands over the xiphoid process in nearly half of the patients. Hand deviation to the epigastric region may occur when the patient is a short-statured or elderly female, and when the rescuer is male.

Assessment of internal thoracic artery patency with transesophageal echocardiography during coronary artery bypass graft surgery.

OBJECTIVE: The purpose of this study was to evaluate intraoperative transesophageal echocardiography (TEE) for assessing patency of internal thoracic artery grafts. DESIGN: A retrospective study. SETTING: A university hospital. PARTICIPANTS: Fifty-one consecutive patients who underwent coronary artery bypass graft (CABG) surgery using the left internal thoracic artery (LITA)-to-left coronary artery were examined postoperatively with coronary angiography (CAG). INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The authors measured blood flow velocity using TEE after anastomosis of a LITA graft. Intraoperative TEE findings and routine CAG results were compared to evaluate the quality of TEE assessment. The LITA was detected in 45 of 51 patients (88%) intraoperatively with TEE. Peak and mean velocities and velocity time integral ratios were determined by dividing each diastolic value by its corresponding systolic value. The peak velocity ratio was 0.51 +/- 0.04 (range, 0.40-0.59) in the presence of stenosis and 1.14 +/- 0.10 (range, 0.58-3.87) in its absence (p = 0.0289), whereas mean velocity ratios were 0.62 +/- 0.05 (range, 0.45-0.72) and 1.27 +/- 0.10 (range, 0.66-4.08) (p = 0.0223), respectively, and velocity time integral ratios were 0.83 +/- 0.09 (range, 0.64-1.05) and 2.69 +/- 0.29 (range, 0.91-8.35) (p = 0.0224), respectively. The critical values for peak and mean velocities and velocity time integral ratios were 0.60, 0.73, and 1.06, respectively, whereas the sensitivity for each was 100% and the specificity was 92%, 94%, and 89%, respectively. CONCLUSIONS: The authors concluded that the intraoperative assessment of LITA patency with TEE was a markedly useful and powerful tool for anesthesiologists during CABG surgery.

Thiamylal and thiopental attenuate beta-adrenergic signaling pathway by suppressing adenylyl cyclase in rat ventricular myocytes.

The effects of intravenous anesthetics on myocytes have not been fully elucidated. To investigate the effects of various intravenous anesthetics such as fentanyl, morphine, ketamine, diazepam, midazolam, thiamylal, and thiopental on the beta-adrenergic signaling pathway, we measured isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) production in freshly isolated rat ventricular myocytes. Fentanyl, morphine, ketamine, diazepam, and midazolam did not significantly affect isoproterenol-stimulated cAMP production. However, thiamylal and thiopental dose-dependently decreased cAMP production stimulated by isoproterenol or by forskolin, a direct adenylyl cyclase stimulator. In addition, we examined the role of protein kinase C (PKC) as a potential mediator of the thiamylal- or thiopental-induced effects on cAMP production using bisindolylmaleimide I, a non-specific PKC inhibitor. Bisindolylmaleimide I did not alter the inhibitory effects of thiamylal or thiopental. Thiamylal and thiopental significantly decreased isoproterenol-stimulated cAMP production by suppressing the adenylyl cyclase. We conclude that barbiturates such as thiamylal and thiopental decrease isoproterenol-stimulated cAMP production by suppressing the adenylyl cyclase through PKC-independent mechanisms.

Prothrombotic roles of substance-P, neurokinin-1 receptors and leukocytes in the platelet-dependent clot formation in whole blood.

A number of types of non-neuronal cells including leukocytes have been confirmed to possess substance-P and its specific neurokinin-1 receptor (NK1R), while the pathophysiological roles of substance-P in these cells remain to be established. Effects of substance-P through NK1R on platelet-dependent clot formation were evaluated by using an oscillating-probe viscoelastometer. The clot signal, indicative of the clot strength in blood-derived samples, was measured after the stimulation with celite and Ca(2+). Substance-P (10 nM) increased the clot signal of whole blood obtained from healthy volunteers, especially modulating the platelet-dependent distinctive peak in traces of the signal. A NK1R antagonist Spantide (500 nM) blocked such substance-P derived change, suggesting the involvement of platelets in the action of substance-P. In contrast, substance-P did not increase the clot signal of platelet-containing but leukocyte-removed plasma. From these, we conclude that substance-P promotes platelet-dependent clot formation through NK1R, in which leukocytes appear to be involved.

Clinically relevant concentrations of olprinone reverse attenuating effect of propofol on isoproterenol-induced cyclic adenosine monophosphate accumulation in cardiomyocytes.

Propofol has been shown to attenuate beta-adrenoreceptor-mediated signal transduction in cardiomyocytes. Cyclic adenosine monophosphate (cAMP) is an essential second messenger of beta-signal transduction, while olprinone, a phosphodiesterase-III inhibitor, improves poor cardiac performance by increasing cAMP levels. In the present study, we investigated the effects of olprinone toward the reducing effect of propofol on beta-adrenoreceptor-mediated increases in cAMP production. First, suspensions of rat ventricular myocytes were incubated with isoproterenol or olprinone and the effects on cAMP concentrations were assessed. Next, propofol was added prior to the addition of isoproterenol or olprinone. Finally, following preincubation with propofol, isoproterenol with or without olprinone was added. Both isoproterenol and olprinone increased cAMP production in a dose-dependent manner. However, clinically relevant concentrations of olprinone (up to 10(-7) M) did not cause a significant increase. Propofol (10(-7)-10(-4) M) attenuated isoproterenol-stimulated increases in cAMP production (decrease of 2 +/- 4% approximately 43 +/- 1%, as compared to the isoproterenol-stimulated state). However, the agent did not alter olprinone (10(-7) M)-stimulated cAMP production. Olprinone (10(-8)-10(-6) M) reversed the attenuating effect of propofol (10(-5) M) toward isoproterenol (10(-7) M)-stimulated cAMP production dose-dependently (increase of 10 +/- 5% approximately 79 +/- 4% as compared to the propofol-attenuated state). Our results suggest that an improvement in cardiac function is provided by olprinone when the beta-adrenoreceptor-mediated signaling pathway is inhibited by propofol.

Systemic glucocorticoid therapy reduces pain and the number of endoneurial tumor necrosis factor-alpha (TNFalpha)-positive mast cells in rats with a painful peripheral neuropathy.

Clinical and experimental evidence suggests that glucocorticoids may be effective in the treatment of neuropathic pain, but their mechanism of action is unknown. We gave triamcinolone (3 mg/kg) to rats with an experimental post-traumatic painful peripheral neuropathy, chronic constriction injury (CCI), five days after nerve injury, when the abnormal pain syndrome is known to be present; and pain sensitivity was measured on postoperative days 7 - 14, a period during which symptoms are known to be at approximately peak severity. Additional CCI rats were treated similarly; and then they were sacrificed five days after the injection for an immunocytochemical analysis of endoneurial tumor necrosis factor-alpha (TNFalpha), macrophages, and mast cells in the sciatic nerve proximal to the site of injury. Vehicle-injected CCI rats demonstrated the expected neuropathic pain symptoms. Triamcinolone-treated CCI rats had a statistically significant reduction in the magnitude of heat-hyperalgesia and mechano-allodynia, but there was no effect on cold-allodynia or mechano-hyperalgesia. On the nerve-injured side of vehicle-injected rats, TNFalpha was present in Schwann cells and mast cells. On the nerve-injured side of triamcinolone-treated rats, there was a significant (71.5%) reduction in the number of TNFalpha-positive mast cells. Our results suggest that glucocorticoid therapy for neuropathic pain may work via the reduced expression of TNFalpha in endoneurial mast cells.

[Use of AirWay Scope for tracheal intubation in bright sunlight].

BACKGROUND: The AirWay Scope (AWS), which is equipped with a wide-angle LCD monitor, has been developed to achieve accurate and safe tracheal intubation under various conditions, including emergency settings. However, since bright sunlight degrades the image quality of LCDs, we investigated its usefulness outdoors in bright sunlight. METHODS: A single anesthesiologist intubated a mannequin with an AWS and conventional direct laryngoscope indoors and in sunlight outdoors, using 6 trials for each condition. Success rate, Cormack grade, and intubation time from device insertion to removal were recorded. RESULTS: Indoors, all tracheal intubations with both devices achieved Cormack grade 1 and were successful. Outdoors, all the laryngoscopes achieved Cormack grade 1 and intubation was successful, whereas intubation with the AWS was successful in 3 trials, while 2 esophageal intubations and 1 failure also occurred. In addition, sunlight deteriorated the image quality of the LCD and Cormack grade could not be determined. The intubation times for the AWS and laryngoscope indoors were 8.7+/-1.8 and 17.0+/-6.5 sec, and outdoors were 18.7+/-9.0 and 21.3+/-4.9 sec, respectively. CONCLUSIONS: Our findings indicate that successful tracheal intubation with an AWS is difficult to achieve in bright sunlight.

[Usability of AirWay Scope for awake tracheal intubation in a burn patient with difficult airway].

The AirWay Scope (AWS; PENTAX Corporation, Tokyo, Japan) is a newly developed rigid video laryngoscope with a built-in LCD monitor that provides accurate verification of tube passage through the vocal cords during tracheal intubation procedures. The blade is shaped to fit the oropharyngeal anatomy, which enables operators to achieve an optimal view for tracheal intubation without requiring alignment of the oral, pharyngeal, and laryngeal axes. We used an AWS for awake intubation in a 34-year-old male burn patient with a difficult airway under conscious sedation obtained with infusion of dexmedetomidine (DEX). Following topical anesthesia of the upper airway and preoxygenation, sedation was induced with 6 microg kg(-1) hr(-1) of DEX for 13 minutes and maintained at 0.5 microg kg(-1) hr(-1). Thereafter, insertion of the AWS gave a Cormack grade 1 glottic view, and endotracheal anesthesia was provided by use of a modified spray tube through the AWS blade without patient anxiety or discomfort. The trachea was intubated using the AWS without respiratory depression or other complications while the patient was sedated (Ramsay sedation scale class 4). We consider the AWS to be useful for awake tracheal intubation in patients with a difficult airway.

Systolic arterial pressure variability reflects circulating blood volume alterations in hemorrhagic shock in rabbits.

Both the high-frequency component of systolic arterial pressure variability and systolic pressure variation (SPV) have been indicated to be strongly affected by respiratory effect and sensitively reflect circulating blood volume (CBV). We attempted to determine the best means reflecting CBV from various parameters using power spectrum analyses of systolic arterial pressure variability (PSSAPV) and heart rate variability (PSHRV), SPV, and pulse pressure variation during graded hemorrhaging and fluid resuscitation. Under isoflurane anesthesia and mechanical ventilation, rabbits in group S (n = 6) had hemorrhaging induced, whereas those in group H (n = 10) had hemorrhaging induced followed by fluid resuscitation. After collecting baseline data, blood was withdrawn at a rate of 1 mL.kg.min for 25 min in both groups, and data were collected at 5 min after bleeding was stopped. Furthermore, in group H, hydroxyethyl starch was continuously infused at a rate of 1 mL.kg.min for 25 min; data were collected at 5 and 60 min after fluid resuscitation. The correlations between CBV and total power (TP, 0.04-2.00 Hz), high-frequency component (0.75-1.40 Hz), and low-frequency component (0.04-0.40 Hz) of PSSAPV were more significant as compared with SPV and pulse pressure variation, whereas no correlations were noted between CBV and PSHRV. To evaluate the regression models appropriately, Akaike information criterion was used, and TP of PSSAPV showed the lowest value. We concluded that TP of PSSAPV most sensitively reflected changes of CBV and that PSSAPV was the most useful parameter for evaluation of volume status as compared with conventional circulatory parameters.

[Dexmedetomidine is a useful concomitant anesthetic agent for perioperative management during tracheobronchial Dumon stent surgery].

We treated 2 patients, 1 undergoing placement and 1 removal of a tracheobronchial Dumon stent, both of whom required preservation of spontaneous breathing during the perioperative period to avoid life-threatening hypoxemia, with dexmedetomidine (DEX) as an anesthetic adjunct. In both cases, anesthesia was induced with 6 microg x kg(-1) x hr(-1) of DEX for 10 minutes and then maintained at 0.4-0.8 microg x kg(-1) x hr(-1), along with a target controlled infusion of propofol combined with intermittent administrations of low-dose fentanyl. Muscle relaxants were avoided and spontaneous breathing was preserved throughout the surgical procedures. The airway was secured using a rigid bronchoscope specific for a Dumon stent procedure. No rescue device, such as high frequency jet ventilation or a percutaneous cardiopulmonary support system, was needed. The perioperative courses were uneventful without any pulmonary or cardiovascular complications. DEX has potent sedative, amnesic, and analgesic properties with a low respiratory depressant effect. Therefore, it is considered useful as a concomitant anesthetic agent for perioperative management of patients who require preservation of spontaneous breathing.

Fulminant-type malignant hyperthermia in Japan: cumulative analysis of 383 cases.

We investigated the transition of clinical signs of fulminant-type malignant hyperthermia (f-MH) by analyzing a database consisting of 383 cumulative cases of f-MH from 1961 to 2004. The cases were divided by time period into group 1 (1961-1984), group 2 (1985-1994), and group 3 (1995-2004). The variables considered were age, sex, type of agents used (succinylcholine and volatile anesthetics), dantrolene administration, clinical signs, laboratory data, and mortality. The level of statistical significance was considered to be less than 5%. Groups 1, 2, and 3 consisted of 196, 127, and 60 cases, respectively. In groups 1, 2, and 3, the rates of dantrolene administration were 18.4%, 93.6%, and 86.7%; the rates of occurrence of ventricular arrhythmia were: 75.2%, 55.6%, and 35.0%; and the rates of generalized muscle rigidity were 64.7%, 60.9%, and 23.9%, respectively. The mortality rate decreased over time, from 42.3% in group 1, to 15.0% in group 2 and group 3. We considered that this decrease occurred because of the increased use of dantrolene and the early diagnosis of malignant hyperthermia in the latter two groups.

[Intracranial subdural hematoma following dural puncture].

BACKGROUND: Intracranial subdural hematoma (SDH) following dural puncture (DP) is a life-threatening complication. However, the characteristics and prognosis are little-known. METHODS: Reports documenting intracranial SDH following DP were surveyed by using PubMed and the Igaku-chuou-zassi (Japana Centra Reveuo Medicina) database (1979-2005) and the cases were analyzed to clarify their characteristics and prognoses. RESULTS: Sixty-nine case reports were enrolled. Seventy per cent of patients underwent anesthetic procedures including spinal and epidural anesthesia. Fifty-two per cent of patients, many of whom receiving obstetrical procedures, were under 40 years of age and majority of the rest of over 40 years were male. Eighty per cent of patients had an onset of SDH within 1 month after DP. Patients often showed disappearance of postural headache, associated with various neurological symptoms such as consciousness disorder, vomiting, hemiplegia and diplopia. The eighty-three per cent of patients recovered completely from SDH except 11 patients who died or afflicted with sequelae because of delayed diagnosis. CONCLUSIONS: Seventy per cent of SDH occured following anesthesia related procedures. Most of them had an onset within one month after DP The prognosis was relatively good as long as SDH could be diagnosed at its early stage. It was necessary to observe the disappearance of postural headache and associated symptoms carefully to avoid delayed diagnosis.

Liver X receptor ligands inhibit the lipopolysaccharide-induced expression of microsomal prostaglandin E synthase-1 and diminish prostaglandin E2 production in murine peritoneal macrophages.

Microsomal prostaglandin E synthase (mPGES)-1, which is dramatically induced in macrophages by inflammatory stimuli such as lipopolysaccharide (LPS), catalyzes the conversion of cyclooxygenase-2 (COX-2) reaction product prostaglandin H(2) (PGH(2)) into prostaglandin E(2) (PGE(2)). The mPGES-1-derived PGE(2) is thought to help regulate inflammatory responses. On the other hand, excess PGE(2) derived from mPGES-1 contributes to the development of inflammatory diseases such as arthritis and inflammatory pain. Here, we examined the effects of liver X receptor (LXR) ligands on LPS-induced mPGES-1 expression in murine peritoneal macrophages. The LXR ligands 22(R)-hydroxycholesterol (22R-HC) and T0901317 reduced LPS-induced expression of mPGES-1 mRNA and mPGES-1 protein as well as that of COX-2 protein. However, LXR ligands did not influence the expression of microsomal PGES-2 (mPGES-2) or cytosolic PGES (cPGES) protein. Consequently, LXR ligands suppressed the production of PGE(2) in macrophages. These results suggest that LXR ligands diminish PGE(2) production by inhibiting the LPS-induced gene expression of the COX-2-mPGES-1 axis in LPS-activated macrophages.

Intrathecally administered COX-2 but not COX-1 or COX-3 inhibitors attenuate streptozotocin-induced mechanical hyperalgesia in rats.

Members of the cyclooxygenase (COX) family are known to catalyze the rate-limiting steps of prostaglandins synthesis and reported to be involved in neuropathic pain. Diabetic neuropathy is a type of neuropathic pain, though it is not clear if COX is relevant to the condition. Recently, spinal COX-2 protein was found to be increasing in streptozotocin-induced rats as compared to the constitutive expression. We attempted to determine which cyclooxygenase isoforms are involved in streptozotocin-induced mechanical hyperalgesia, which was induced by a single intraperitoneal injection of 75 mg/kg of streptozotocin. Intrathecal administrations of the COX-2 inhibitors SC-58125 (7-100 microg) and NS-398 (7-60 microg), as well as a high dose (100 microg) of the COX-1 inhibitor SC-560 attenuated hyperalgesia, whereas intrathecal administrations of a low dose (10 microg) of SC-560 and the COX-3 inhibitor acetaminophen (1-7 mg) did not. Further, intrathecal administration of SC-58125 (100 microg) did not produce an analgesic effect in normal rats. These results indicate that intrathecal administration of COX-2 inhibitors has an anti-hyperalgesic effect on streptozotocin-induced mechanical hyperalgesia and we concluded that spinal COX-2 is pivotal in streptozotocin-induced hyperalgesia.

[Validity of intraoperative administration of dexmedetomidine in a patient with dermatomyositis-derived respiratory failure].

A 66-year-old female with dermatomyositis and severe respiratory failure from collagen lungs, dependent on domiciliary oxygen therapy, was scheduled for a mastectomy. Anesthesia was induced with dexmedetomidine (DEX) 6 microg x kg(-1) x h(-1) for 10 minutes and maintained at 0.7 microg x kg(-1) x h(-1), along with a target controlled infusion of propofol combined with epidural anesthesia. No narcotic or muscle relaxant was used. The airway was secured using a laryngeal mask airway and spontaneous breathing was preserved. The perioperative course was uneventful without any pulmonary complications. DEX has a certain analgesic property and a mild respiratory depressant effect. Therefore, it is considered useful as a concomitant anesthetic agent for perioperative management of patients with respiratory failure.

[Evaluation of the sedation level with propofol with electroencephalographic Entropy in comparison with bispectral index monitor].

BACKGROUND: Entropy, a newly available electroencephalographic monitor, demonstrates two parameters, response entropy (RE) and state entropy (SE). The aim of this study is to compare RE and SE with bispectral index (BIS) during anesthetic induction with propofol. METHODS: Fifteen patients received target controlled infusion of propofol starting at 3 microg x ml(-1). We measured RE, SE and BIS and recorded effect-site concentrations of propofol at three sedation levels: VR1; conscious state before infusion of propofol, VR2; no response to verbal command, and VR3; no response to verbal command and shaking. Spearman rank correlations and prediction probability for sedation level were analyzed. RESULTS: Effect-site concentrations of propofol at VR1, VR2, and VR3 were 0, 1.8 +/- 0.7, and 2.4 +/- 0.7, respectively. All three parameters showed significant correlations with sedation levels. Prediction probability values of SE, RE, and BIS were 0.905, 0.894, and 0.890, respectively. CONCLUSIONS: Response entropy and SE can provide similar information as BIS about the sedation level with propofol.

Synthetic peroxisome proliferator-activated receptor-gamma agonists restore impaired vasorelaxation via ATP-sensitive K+ channels by high glucose.

The present study was designed to examine whether in the human artery, synthetic peroxisome proliferator-activated receptor (PPAR)-gamma agonists restore vasorelaxation as well as hyperpolarization via ATP-sensitive K+ channels impaired by the high concentration of D-glucose and whether the restoration may be mediated by the antioxidant capacity of these agents. The isometric force and membrane potential of human omental arteries without endothelium were recorded. The production rate of superoxide was evaluated using a superoxide-generating system with xanthine-xanthine oxidase in the absence of smooth muscle cells. Glibenclamide abolished vasorelaxation and hyperpolarization in response to levcromakalim. Addition of D-glucose (20 mM) but not L-glucose (20 mM) reduced this vasorelaxation and hyperpolarization. Synthetic PPAR-gamma agonists (troglitazone and rosiglitazone) and/or an inhibitor of superoxide generation (4,5-dihydroxy-1,3-benzene-disulfonic acid, Tiron), but not a PPAR-alpha agonist (fenofibrate), restored vasorelaxation and hyperpolarization in response to levcromakalim in arteries treated with D-glucose. Troglitazone and rosiglitazone, but not fenofibrate, decreased the production rate of superoxide without affecting uric acid generation. These findings suggest that synthetic PPAR-gamma agonists recover the function of ATP-sensitive K+ channels reduced by the high concentration of glucose in human vascular smooth muscle cells and that the effect of these agonists may be mediated in part by their antioxidant capacity.

[Anesthetic management of laser surgery with bronchial stenting for a tracheal tumor].

Anesthetic management during surgery for a tracheal tumor is extremely difficult in terms of airway management. We managed a patient with a tracheal tumor who was successfully treated without complication. The trachea of a 66-year-old woman was narrowed by a tumor to one-third of its original diameter, for which Nd-YAG laser surgery with insertion of an intratracheal Dumon stent was performed. Anesthesia was maintained with neuroleptanalgesia using fentanyl and droperidol, supplemented with a TCI infusion of propofol under spontaneous breathing. High frequency jet ventilation (HFJV) was prepared for intraoperative poor oxygenation and/or ventilation. The patient was able to maintain a good respiratory condition throughout the operation without special respiratory support, including use of HFJV. We conclude that the maintenance of spontaneous breathing is essential for anesthetic management in the present case, while an intraoperative airway strategy based on the preoperative breathing condition of the patient is also important.

General anesthesia for patient with type III homocystinuria (tetrahydrofolate reductase deficiency).

Homocystinuria, a rare autosomal recessive genetic disease, is generally classified into 3 types (types I-III). Extremely rare type III is from a defect of the enzyme tetrahydrofolate reductase which converts homocysteine to methionine. The anesthetic problem of type III homocystinuria is the elevation of serum homocysteine and the deficiency of essential amino acid methionine, which result in the perioperative thromboembolic events and nitrous oxide-induced neurological impairment. We provided successful anesthetic management for a patient with type III homocystinuria, during which we were careful to take measures against perioperative thromboembolism and did not use nitrous oxide.

Suppression of inducible nitric oxide synthase and cyclooxygenase-2 gene expression by 22(R)-hydroxycholesterol requires de novo protein synthesis in activated macrophages.

Liver X receptors (LXRs) play an important role in lipid metabolism. Recently, a role for these proteins was identified in suppressing the inflammatory response. However, it is not known whether the natural ligands of LXRs, e.g. 22(R)-hydroxycholesterol (22R-HC), can suppress the inflammatory response after the onset of inflammation. We demonstrate here that treatment of Lipopolysaccharide (LPS)-activated RAW264.7 macrophages with 22R-HC markedly suppressed nitric oxide (NO) production and inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression. Additionally, 22R-HC did not affect the DNA binding activity of NF-kappaB, AP-1 and C/EBP(s), important transcriptional factors for iNOS and COX-2 genes expression. Furthermore iNOS and COX-2 mRNA suppression by 22R-HC was diminished by cellular treatment with cycloheximide. These results suggest that 22R-HC suppresses the expression of iNOS and COX-2 genes through de novo protein synthesis of an unidentified protein in LPS-activated macrophages.