Effect of the allelic variants of ABCB1, CYP2D6 and HTR3B on response of ramosetron to prevent chemotherapy-induced nausea and vomiting in Korean cancer patients.

AIM: Despite appropriate use of antiemetics including 5-hydroxytryptamine type 3 (5-HT3 ) receptor antagonists, chemotherapy-induced nausea and vomiting (CINV) is still an unsolved problem in patients with anticancer drugs. We examined whether the variants of ABCB1, CYP2D6 and HTR3B affect efficacy of ramosetron, a selective 5-HT3 receptor antagonist in a dose escalation clinical trial. METHODS: We conducted a clinical trial on patients who underwent FOLFOX combination chemotherapy. The participants were randomized into three groups of ramosetron: 0.3 mg (standard dose), 0.45 mg and 0.6 mg. Rhodes index of nausea, vomiting and retching were measured at 1, 6 h, day 1, day 2 and day 7 after the administration of ramosetron as a clinical parameter of CINV and polymorphism was analyzed from genomic DNA. RESULTS: There was a dose-dependent decrease in the nausea and vomiting scores at day 1 and day 2, not statistically significant. The Rhodes index of nausea, vomiting and retching score at day 1 in participants with HTR3B-100_-102delAAG deletion variants was significantly higher than wild type participants, regardless of dosages. However, the polymorphisms including ABCB1, CYP2D6 and other HTR3B genes did not affect response to ramosetron after chemotherapy. CONCLUSION: These results suggest that the -AAG deletion variant of the 5-HT3B receptor gene may contribute to variability in response to antiemetic therapy for CINV regardless of dose escalation. These results suggest that carrying a -100_-102delAAG variant of 5-HT3 gene should be supported by alternate or additive antiemetics in addition to 5-HT3 antagonists to control acute emesis.

Population pharmacokinetics and prophylactic anti-emetic efficacy of ramosetron in surgical patients.

AIMS: This study characterized the pharmacokinetics of ramosetron and compared prophylactic anti-emetic efficacy with that of ondansetron in a large population. METHODS: Fifty-eight patients consented to the pharmacokinetic analysis and were assigned randomly to receive 0.3, 0.45 or 0.6 mg ramosetron after induction of anaesthesia. Blood samples were acquired at preset intervals. Non-compartmental and population pharmacokinetic analyses were performed. In total, 1102 patients consented to the evaluation of prophylactic anti-emetic efficacy and were allocated randomly to receive 0.3 mg ramosetron or 4 mg ondansetron at the end of surgery. An additional 16 mg ondansetron were mixed in the intravenous patient-controlled analgesia pump of the ondansetron group. Post-operative nausea and vomiting (PONV) were evaluated 6, 24 and 48 h post-operatively using the Rhodes index of nausea, vomiting and retching (RINVR). Administration of rescue anti-emetics and adverse events were evaluated. RESULTS: The pharmacokinetic parameter estimates were V1 (l) = 5.12, V2 (l) = 108, CL (l⋅min(-1) ) = 0.08 + (59⋅age(-1) ) × 0.09, Q (l⋅min(-1) ) = 1.42. The incidences of PONV in the ramosetron and ondansetron groups were 77 (13.9%) and 113 (20.6%) and 44 (7.9%) and 66 (12.0%) at 24 and 48 h post-operatively, respectively (P = 0.004, 0.030). RINVR was significantly lower in the ramosetron than the ondansetron group 24 and 48 h post-operatively (P = 0.003, 0.025). Use of rescue anti-emetics and incidence of adverse events were comparable. CONCLUSIONS: A two compartment mammillary model was used to describe ramosetron pharmacokinetics. Prophylactic anti-emetic efficacy of ramosetron was significantly better 24 and 48 h post-operatively than that of ondansetron, particularly when the Apfel score was ≥ 3.

Effect of curcumin (Curcuma longa extract) on LPS-induced acute lung injury is mediated by the activation of AMPK.

PURPOSE: Curcumin, a biphenolic compound extracted from turmeric (Curcuma longa), possesses potent anti-inflammatory activity. The present study investigated whether curcumin could increase 5' adenosine monophosphate-activated protein kinase (AMPK) activity in macrophages and modulate the severity of lipopolysaccharide (LPS)-induced acute lung injury. METHODS: Macrophages were treated with curcumin and then exposed (or not) to LPS. Acute lung injury was induced by intratracheal administration of LPS in BALB/c mice. RESULTS: Curcumin increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in a time- and concentration-dependent manner. Curcumin did not increase phosphorylation of liver kinase B1, a primary kinase upstream of AMPK. STO-609, an inhibitor of calcium(2+)/calmodulin-dependent protein kinase kinase, diminished curcumin-induced AMPK phosphorylation, but transforming growth factor-beta-activated kinase 1 inhibitor did not. Curcumin also diminished the LPS-induced increase in phosphorylation of inhibitory κB-alpha and the production of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein (MIP)-2, and interleukin (IL)-6 by macrophages. Systemic administration of curcumin significantly decreased the production of TNF-α, MIP-2, and IL-6 as well as neutrophil accumulation in bronchoalveolar lavage fluid, and also decreased pulmonary myeloperoxidase levels and the wet/dry weight ratio in mice subjected to LPS treatment. CONCLUSION: These results suggest that the protective effect of curcumin on LPS-induced acute lung injury is associated with AMPK activation.

Spinal 5-HT1A, not the 5-HT1B or 5-HT3 receptors, mediates descending serotonergic inhibition for late-phase mechanical allodynia of carrageenan-induced peripheral inflammation.

Previous electrophysiological studies demonstrated a limited role of 5-hydroxytryptamine 3 receptor (5-HT3R), but facilitatory role of 5-HT1AR and 5-HT1BR in spinal nociceptive processing of carrageenan-induced inflammatory pain. The release of spinal 5-HT was shown to peak in early-phase and return to baseline in late-phase of carrageenan inflammation. We examined the role of the descending serotonergic projections involving 5-HT1AR, 5-HT1BR, and 5-HT3R in mechanical allodynia of early- (first 4h) and late-phase (24h after) carrageenan-induced inflammation. Intrathecal administration of 5-HT produced a significant anti-allodynic effect in late-phase, but not in early-phase. Similarly, intrathecal 5-HT1AR agonist (8-OH-DPAT) attenuated the intensity of late-phase allodynia in a dose dependent fashion which was antagonized by 5-HT1AR antagonist (WAY-100635), but produced no effect on the early-phase allodynia. However, other agonists or antagonists of 5-HT1BR (CP-93129, SB-224289) and 5-HT3R (m-CPBG, ondansetron) did not produce any anti- or pro-allodynic effect in both early- and late- phase allodynia. These results suggest that spinal 5-HT1A, but not 5-HT1B or 5-HT3 receptors mediate descending serotonergic inhibition on nociceptive processing of late-phase mechanical allodynia in carrageenan-induced inflammation.

Blood lead concentration and related factors in Korea from the 2008 National Survey for Environmental Pollutants in the Human Body.

This study evaluated blood lead concentrations in the Korean general population and the correlation between various exposure sources using data from the 2008 Korea National Survey for Environmental Pollutants in the Human Body (National Institute of Environmental Research, Korea). The general and occupational characteristics were gathered from 5136 participants who were 20 years of age and older using a structured questionnaire. Blood lead concentrations were analyzed using an atomic absorption spectrophotometer. Statistical analysis was performed using multiple linear regressions of the log lead concentrations to the independent variables such as age, gender, smoke, herbal medication and drug consumption, drinking water, and living area. Geometric mean (GM) blood lead concentrations in Korean adults were 19.7 µg/l. The blood lead concentrations increased with age; the highest concentrations were found in the 50-69-year age group (p<0.001). Males were higher than in females (p<0.001). Current smokers and drinkers had higher concentrations than nonsmokers (p<0.001) and nondrinkers (p<0.001), respectively. People who took herbal medication and drug consumption were higher than those who did not (p<0.001). Education level was negatively associated with blood lead concentration (p<0.001). People living in or around industrial areas had elevated blood lead concentration (p<0.001). Family income was also negatively associated with lead concentration, but not significantly. For drinking water, the underground water (spring or well water) drinking group had higher concentrations than other types of water drinking groups, but not significantly (p=0.063). The blood lead concentrations by occupation were significant (p<0.034): the highest was in laborer and Agricultural-Fishery-Forestry and the lowest in office workers. In women, blood lead concentrations tended to decrease with increasing delivery times, but not significantly. The blood lead concentration (GM) of the general adult population in Korea has decreased over time from 45.8 µg/l (1999) to 19.7 µg/l (2008). Although it is still higher than in other countries such as the United States and Canada, it is rapidly decreasing. Gender, age, smoking and alcohol drinking status, herbal medication and drug consumption, education level, living area and occupation were significantly related to the blood lead concentrations in Korea.

Postoperative nausea and vomiting after total thyroidectomy: sevoflurane combined with prophylactic ramosetron vs. propofol-based total intravenous anesthesia.

BACKGROUND: The frequent and distressing adverse events (AEs) of postoperative nausea and vomiting (PONV) are of major concern in 63-84% of adult patients undergoing thyroidectomy. We conducted this prospective study to compare two prophylactic strategies; sevoflurane combined with ramosetron and propofol-based total intravenous anesthesia in a homogenous group of non-smoking women undergoing total thyroidectomy. METHODS: In the current prospective study, we enrolled a consecutive series of 64 female patients aged between 20 and 65 years with an American Society of Anesthesiologists physical status of I or II who were scheduled to undergo elective total thyroidectomy under general anesthesia. Patients were randomized to either the SR (sevoflurane and remifentanil) group or the TIVA group. We evaluated the incidence and severity of PONV, the use of rescue anti-emetics and the severity of pain during the first 24 h after surgery. RESULTS: There were no significant differences in the proportion of the patients with a complete response and the Rhodes index, including the occurrence score, distress score and experience score, between the two groups. In addition, there were no significant differences in the proportion of the patients who were in need of rescue anti-emetics or analgesics and the VAS scores between the two groups. CONCLUSIONS: In conclusion, TIVA and ramosetron prophylaxis reduced the expected incidence of PONV in women undergoing total thyroidectomy. In addition, there was no significant difference in the efficacy during the first 24 h postoperatively between the two prophylactic regimens.

High lead exposure in two leaded bronze ingot foundry workers.

BACKGROUND: Awareness about lead poisoning in South Korea has increased; however, occupational exposures occurring in small-scale businesses have not been thoroughly investigated. We report two cases of high lead exposure in a leaded bronze ingot foundry. CASE PRESENTATION: Two employees, a 54-year-old primary operator and a 46-year-old assistant, at a small-scale metalworking company who had been employed for 18 years and 1 month, respectively, showed elevated blood lead levels (61.1 µg/dL and 51.7 µg/dL, respectively) at an occupational health checkup. Neither worker complained of abnormal symptoms nor signs related to lead poisoning. Health assessment follow-ups were conducted and biological exposure indices of lead were calculated every four weeks. After the initial follow-up assessment, both workers were relocated from the foundry process to the metalworking process. In addition, a localized exhaust system was installed after the second follow-up. CONCLUSIONS: Foundry workers in a small-scale businesses might be at high risk of lead exposure because these businesses might be vulnerable to poor industrial hygiene. Therefore, regular occupational health checkups are required.

Anesthetic requirements and stress hormone responses in chronic spinal cord-injured patients undergoing surgery below the level of injury: nitrous oxide vs remifentanil.

BACKGROUND: Nitrous oxide (N2O) and remifentanil both have anesthetic-reducing and antinociceptive effects. We aimed to determine the anesthetic requirements and stress hormone responses in spinal cord-injured (SCI) patients undergoing surgery under sevoflurane anesthesia with or without pharmacodynamically equivalent doses of N2O or remifentanil. METHODS: Forty-five chronic, complete SCI patients undergoing surgery below the level of injury were randomly allocated to receive sevoflurane alone (control, n = 15), or in combination with 67% N2O (n = 15) or target-controlled infusion of 1.37 ng/ml remifentanil (n = 15). Sevoflurane concentrations were titrated to maintain a Bispectral Index (BIS) value between 40 and 50. Measurements included end-tidal sevoflurane concentrations, mean arterial blood pressure (MAP), heart rate (HR), and plasma catecholamine and cortisol concentrations. RESULTS: During surgery, MAP, HR, and BIS did not differ among the groups. Sevoflurane concentrations were lower in the N2O group (0.94 ± 0.30%) and the remifentanil group (1.06 ± 0.29%) than in the control group (1.55 ± 0.34%) (P < 0.001, both). Plasma concentrations of norepinephrine remained unchanged compared to baseline values in each group, with no significant differences among groups throughout the study. Cortisol levels decreased during surgery as compared to baseline values, and returned to levels higher than baseline at 1 h after surgery (P < 0.05) without inter-group differences. CONCLUSIONS: Remifentanil (1.37 ng/ml) and N2O (67%) reduced the sevoflurane requirements similarly by 31-39%, with no significant differences in hemodynamic and neuroendocrine responses. Either remifentanil or N2O can be used as an anesthetic adjuvant during sevoflurane anesthesia in SCI patients undergoing surgery below the level of injury.

Effects of inspired oxygen fraction in discriminating venous from arterial blood in percutaneous central venous catheterization under general anesthesia.

BACKGROUND: A low fraction of inspired oxygen (FiO(2)) increases venous deoxygenated hemoglobin concentrations, making the color of the blood darker. The present study was aimed to determine the effects of FiO(2) on the ability to discriminate venous from arterial blood. METHODS: One-hundred and sixty surgical patients undergoing percutaneous central venous access of the internal jugular vein were randomly assigned to receive an FiO(2) of 0.2, 0.4, 0.6, or 1.0 (n = 40 each) for at least 20 min prior to central line placement under general anesthesia. Vascular access was achieved with a 22-gauge needle; 2 ml of blood was withdrawn and shown to three physicians including the operator. Each of them was asked to identify the blood as 'arterial', 'venous' or 'not sure'. Simultaneous blood gas analysis of the samples was performed on blood taken from the puncture site and the artery after visual comparison to confirm blood's origin and hemodynamic measurements. RESULTS: Lowering FiO(2) progressively increased venous deoxygenated hemoglobin concentrations (2.24 ± 1.12, 3.30 ± 1.08, 3.66 ± 1.15, and 3.71 ± 1.33 g/dl) in groups having an FiO(2) of 1.0, 0.6, 0.4 and 0.2, respectively (P < 0.001), thereby facilitating the 'venous' blood identification (P < 0.001). Neither heart rate nor mean arterial pressure differed among the groups. None developed hypoxemia (percutaneous hemoglobin oxygen saturation < 90%) in any group during the study period. CONCLUSIONS: A low FiO(2) increases venous deoxygenated hemoglobin levels, thereby facilitating the recognition by clinicians of its venous origin in percutaneous central venous catheterization under general anesthesia.

Postoperative nausea and vomiting after mastoidectomy with tympanoplasty: a comparison between TIVA with propofol-remifentanil and balanced anesthesia with sevoflurane-remifentanil.

BACKGROUND: There is growing interest in the anesthetic approach using total intravenous anesthesia (TIVA) with propofol and remifentanil for the prevention of postoperative nausea and vomiting (PONV). The aim of this study was to compare between the two anesthetic techniques for preventing PONV in the patients undergoing mastoidectomy with tympanoplasty. METHODS: After obtaining informed consent, 62 patients aged between 20 to 60 years undergoing elective mastoidectomy and tympanoplasty were randomized into two equal study groups: group P/R (n = 31) included patients undergoing TIVA with propofol and remifentanil, and group S/R (n = 31) included patients undergoing balanced anesthesia with sevoflurane and remifentanil. The incidences of PONV and complete response (no PONV, no rescue) were assessed at 1 and 24 h after surgery, using the Rhodes Index. Also, the usage of rescue antiemetics and pain intensity were recorded. RESULTS: The Rhodes Index including the occurrence score, distress score and experience score was significantly lower in the P/R group compared to that in the S/R group during the study period (P < 0.05), and the incidence of complete response was significantly higher in the P/R group compared to that in the S/R group, during the first 24 h after surgery. 4 patients in the S/R group requested antiemetics during the first 1 h after surgery. There were no significant differences in pain intensity among groups. CONCLUSIONS: Compared to balanced anesthesia with sevoflurane and remifentanil, TIVA with propofol and remifentanil was followed by significantly lower incidence and severity of PONV.

The effect of priming injection of different doses of remifentanil on injection pain of microemulsion propofol premixed with lidocaine.

BACKGROUND: The injection pain of microemulsion propofol is frequent and difficult to prevent. This study examined the prevention of pain during microemulsion propofol injection by pretreatment with different doses of remifentanil or saline, and premixing of lidocaine. METHODS: One hundred sixty ASA physical status 1-2 adult patients scheduled for elective surgery were enrolled into one of four groups (n = 40, in each). The patients received saline (group LS), remifentanil 0.3 µg/kg (group LR 0.3), remifentanil 0.5 µg/kg (group LR 0.5), or remifentanil 1.0 µg/kg (group LR 1.0), and after 90 seconds received an injection of 2 mg/kg microemulsion propofol premixed with lidocaine 40 mg. Pain was assessed on a four-point scale during microemulsion propofol injection. RESULTS: The incidence of microemulsion propofol-induced pain was significantly lower in the LR 0.3, LR 0.5 and LR 1.0 groups than in the LS group (37.5%, 12.5% and 10% vs 65%, respectively). The LR 0.5 and LR 1.0 groups showed significantly less frequent and intense pain than the LR 0.3 group. However, both incidence and severity of pain were not different between LR 0.5 and LR 1.0 groups. CONCLUSIONS: The combination of remifentanil and lidocaine is effective in alleviating pain associated with a microemulsion propofol injection compared with just lidocaine. Remifentanil 0.5 µg/kg had a similar analgesic effect compared to the 1.0 µg/kg dose.

Beta-1 selective adrenergic antagonist landiolol and esmolol can be safely used in patients with airway hyperreactivity.

This study was undertaken to clarify the effects of esmolol and landiolol, beta-1 selective adrenergic antagonists, on hyperreactive airways in both ovalbumin-sensitized guinea pigs and asthmatic patients. In the animal study, asthma was induced by ovalbumin. After control acetylcholine responses for total pulmonary resistance (Raw) and dynamic lung compliance (Cdyn) were obtained, the animals received propranolol, esmolol, or landiolol, and the same protocol was again performed. Sixty inpatients with coronary risk factors and asthma were enrolled in the human study. Under propofol anesthesia, the patients received saline, esmolol, or landiolol. To assess intubation-induced bronchoconstriction, the presence of wheezing was determined. The dose-response curves of Raw and Cdyn to acetylcholine were significantly elevated and declined in the ovalbumin-sensitized model compared with those in the control group. Neither esmolol nor landiolol had any effect on the acetylcholine-induced response curve in these sensitized animals. However, propranolol significantly enhanced Raw and reduced Cdyn in this model. Tracheal intubation increased the incidence of wheezing in asthmatic patients. However, there was no significant difference in the incidence of wheezing among these groups. The ultra-short-acting beta-1 selective adrenergic antagonists esmolol and landiolol can be safely used perioperatively in patients with airway hyperreactivity.

Maternal and neonatal effects of remifentanil used during induction of general anesthesia in preeclamptic patients undergoing cesarean delivery.

BACKGROUND: Endotracheal intubation elicits cardiovascular and arousal responses. The present study was aimed to determine whether remifentanil affects these responses in patients with preeclampsia. METHODS: Thirty preeclamptic women who were scheduled to undergo cesarean delivery under general anesthesia were randomly assigned to receive either remifentanil 1 microgram/kg (n = 15) or saline (n = 15) before induction of anesthesia. Systolic arterial pressure (SBP), heart rate (HR) and bispectral index (BIS) value as well as plasma catecholamine concentrations were measured. Neonatal effects were assessed using Apgar score and umbilical cord blood gas analysis. RESULTS: Induction with thiopental caused a reduction in SBP and BIS (P < 0.01) in both groups. Following the tracheal intubation SBP and HR increased in both groups, the magnitude of which was lower in the remifentanil group. BIS values also increased, of which magnitude did not differ between the groups. Norepinephrine concentrations increased significantly following the intubation in the control, while remained unaltered in the remifentanil group. The neonatal Apgar scores (5 min), and umbilical gas values were similar in the two groups except for higher incidence of Apgar score < 7 at 1 min in the remifentanil group. CONCLUSIONS: Remifentanil 1 microgram/kg effectively attenuates hemodynamic and catecholamine but not BIS responses to tracheal intubation in preeclamptic patients undergoing cesarean delivery. However, remifentanil may cause mild neonatal depression and thus should be used when adequate facilities for neonatal resuscitation are available.

Removal of heavy metals using waste eggshell.

The removal capacity of toxic heavy metals by the reused eggshell was studied. As a pretreatment process for the preparation of reused material from waste eggshell, calcination was performed in the furnace at 800 degrees C for 2 h after crushing the dried waste eggshell. Calcination behavior, qualitative and quantitative elemental information, mineral type and surface characteristics before and after calcination of eggshell were examined by thermal gravimetric analysis (TGA), X-ray fluorescence (XRF), X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. After calcination, the major inorganic composition was identified as Ca (lime, 99.63%) and K, P and Sr were identified as minor components. When calcined eggshell was applied in the treatment of synthetic wastewater containing heavy metals, a complete removal of Cd as well as above 99% removal of Cr was observed after 10 min. Although the natural eggshell had some removal capacity of Cd and Cr, a complete removal was not accomplished even after 60 min due to quite slower removal rate. However, in contrast to Cd and Cr, an efficient removal of Pb was observed with the natural eggshell rather than the calcined eggshell. From the application of the calcined eggshell in the treatment of real electroplating wastewater, the calcined eggshell showed a promising removal capacity of heavy metal ions as well as had a good neutralization capacity in the treatment of strong acidic wastewater.

Electroencephalographic approximate entropy changes in healthy volunteers during remifentanil infusion.

BACKGROUND: The aim of this study was to investigate the independent effect of remifentanil on the approximate entropy (ApEn) in frontoparietal montages. The authors investigated which montages were relevant to assess the remifentanil effect on the electroencephalogram. Spectral edge frequency and the canonical univariate parameter were used as comparators. METHODS: Twenty-eight healthy volunteers were enrolled. With recording of the electroencephalogram at the F3, F4, Cz, P3, and P4 montages, remifentanil was infused at the rate of 1-8 mug . kg . min for 15-20 min. The relation between remifentanil concentration and the electroencephalographic parameters were tested by Spearman correlation. Signal-to-noise ratio, artifact robustness, coefficient of variation of the median baseline and maximal electroencephalographic effects, and ratio of average maximal electroencephalographic effect to interindividual baseline variability were measured. The performance of ApEn as an index of remifentanil effect site concentrations was tested by prediction probability. RESULTS: Approximate entropy showed significant correlation (R = -0.6465, P < 0.0001) with remifentanil concentration. It provided comparable signal-to-noise ratio, artifact robustness, and ratio of average maximal electroencephalographic effect to interindividual baseline variability to 95% spectral edge frequency. The coefficients of variation of the median baseline and maximal electroencephalo graphic effects were smallest in ApEn. Parietal montages showed higher ratios of average maximal electroencephalographic effect to interindividual baseline variability for all electroencephalographic parameters and lower coefficients of variation of the baseline values for ApEn and 95% spectral edge frequency than frontal montages. The prediction probability of ApEn was 0.7730. CONCLUSIONS: Approximate entropy derived from a parietal montage is appropriate for the assessment of the remifentanil effect on the electroencephalogram.

Antinociceptive effects and synergistic interaction with morphine of intrathecal metabotropic glutamate receptor 2/3 antagonist in the formalin test of rats.

Spinal metabotropic glutamate receptors (mGluRs) have been known to be involved in the modulation of nociception. While the antinociceptive effects of the mGluR1/5 have been demonstrated, the role of mGluR2/3 for nociception is less clear. This study investigated the effects of an intrathecal mGluR2/3 agonist, APDC, and a mGluR2/3 antagonist, LY341495, for inflammatory and acute pain in the formalin test and thermal stimulation test. We also examined their interaction with intrathecal morphine for the antinociceptive effect. APDC had little effect on the formalin-induced nociception. In contrast, LY341495 caused a dose-dependent suppression of the phase 2 flinching response to the formalin stimulus without affecting phase 1 flinching response. Furthermore, the suppression of pain behavior by LY341495 during phase 2 was reduced significantly by pretreatment with APDC. LY341495 and morphine also showed synergistic drug interaction for antinociception during phase 2 in the formalin test.

Evaluation of interaction between intrathecal adenosine and MK801 or NBQX in a rat formalin pain model.

Adenosine and excitatory amino acids have been known to be involved in modulating nociceptive transmission at the spinal level. The authors assessed the characteristics of the interaction of the adenosine-excitatory amino acid antagonist combinations in the spinal cord of rats on the formalin-induced nociception. Intrathecal NMDA antagonist ((5R, 10S)-(+)-5-methyl-10,11-dihydro-(5)H-dibenzo[a[,]d]cyclohepten-5,10-imine hydrogen maleate, MK801, 30 microg) and AMPA antagonist (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[F]quinoxaline-7-sulfonamide, NBQX, 3 microg) decreased the total number of flinches during both phases in the formalin test. Intrathecal adenosine (300 microg) had little effect on the phase 1 flinching response, but decreased the phase 2 response. The fixed dose analysis and the isobolographic analysis revealed that adenosine interacts additively with MK801 and NBQX in the spinal cord.

Lack of the nitric oxide-cyclic GMP-potassium channel pathway for the antinociceptive effect of intrathecal zaprinast in a rat formalin test.

Zaprinast is a phosphodiesterase inhibitor that is active in various models of pain when administered locally. In addition, the antinociception of zaprinast is involved in the nitric oxide (NO)-cGMP pathway. However, the effect of zaprinast administered spinally has not been examined. Therefore, this study examined the effect of zaprinast on the formalin-induced nociception at the spinal level. Next, the role of the NO-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Catheters were inserted into the intrathecal space of male Sprague-Dawley (SD) rats. Pain was induced by applying 50 microl of a 5% formalin solution to the hindpaw. The change in the zaprinast-induced effect was examined after an intrathecal pretreatment with a NO synthase inhibitor (l-NMMA), a guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide). Zaprinast produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Intrathecal l-NMMA, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase of the formalin test. These results suggest that zaprinast is effective against both acute pain and the facilitated pain state at the spinal level. However, the NO-sensitive cGMP-potassium channel pathway is not contributable to the antinociceptive mechanism of zaprinast in the spinal cord.

CT in blunt liver trauma.

Nonsurgical treatment has become the standard of care in hemodynamically stable patients with blunt liver trauma. The use of helical computed tomography (CT) in the diagnosis and management of blunt liver trauma is mainly responsible for the notable shift during the past decade from routine surgical to nonsurgical management of blunt liver injuries. CT is the diagnostic modality of choice for the evaluation of blunt liver trauma in hemodynamically stable patients and can accurately help identify hepatic parenchymal injuries, help quantify the degree of hemoperitoneum, and reveal associated injuries in other abdominal organs, retroperitoneal structures, and the gastrointestinal tract. The CT features of blunt liver trauma include lacerations, subcapsular or parenchymal hematomas, active hemorrhage, juxtahepatic venous injuries, periportal low attenuation, and a flat inferior vena cava. It is important that radiologists be familiar with the liver injury grading system based on these CT features that was established by the American Association for the Surgery of Trauma. CT is also useful in the assessment of delayed complications in blunt liver trauma, including delayed hemorrhage, hepatic or perihepatic abscess, posttraumatic pseudoaneurysm and hemobilia, and biliary complications such as biloma and bile peritonitis. Follow-up CT is needed in patients with high-grade liver injuries to identify potential complications that require early intervention.