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ABSTRACT: Although paclitaxel is a widely used chemotherapeutic agent for the treatment of solid cancers, side effects such as neuropathic pain lead to poor compliance and discontinuation of the therapy. Ethyl pyruvate (EP) is known to have analgesic effects in several pain models and may inhibit apoptosis. The present study was designed to investigate the analgesic effects of EP on mechanical allodynia and apoptosis in dorsal root ganglion (DRG) cells after paclitaxel administration.
Rats were randomly divided into 3 groups: 1) a control group, which received only vehicle; 2) a paclitaxel group, which received paclitaxel; and 3) an EP group, which received EP after paclitaxel administration. Mechanical allodynia was tested before and at 7 and 14 days after final paclitaxel administration. Fourteen days after paclitaxel treatment, DRG apoptosis was determined by activated caspase-3 immunoreactivity (IR).
Post-treatment with EP did not significantly affect paclitaxel-induced allodynia, although it tended to slightly reduce sensitivities to mechanical stimuli after paclitaxel administration. After paclitaxel administration, an increase in caspase-3 IR in DRG cells was observed, which was co-localized with NF200-positive myelinated neurons. Post-treatment with EP decreased the paclitaxel-induced caspase-3 IR. Paclitaxel administration or post-treatment with EP did not alter the glial fibrillary acidic protein IRs in DRG cells.
Inhibition of apoptosis in DRG neurons by EP may not be critical in paclitaxel-induced mechanical allodynia.
The Korean journal of pain 04/2013; 26(2):135-41.
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Korean journal of anesthesiology 03/2013; 64(3):286-7.
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ABSTRACT: It has been demonstrated that the expression of tumor necrosis factor-α (TNF-α) and apoptotic cell death in the dorsal root ganglion (DRG) following spinal nerve constriction injury play a role in the initiation and continuation of hyperalgesia and allodynia. The present study was designed to investigate the effects of ethyl pyruvate (EP) on mechanical and cold allodynia, TNF-α expression, and apoptosis in DRG after spinal nerve ligation injury.
Rats were divided into 3 groups: control, pre-EP, and post-EP. EP (50 mg/kg) was intraperitoneally injected 30 minutes before (pre-EP) or after (post-EP) surgery. Behavioral tests to determine mechanical and cold allodynia were conducted before surgery and 4 and 7 days after surgery. Seven days after surgery, TNF-α protein levels in DRG were evaluated by enzyme-linked immunosorbent assay, and DRG apoptosis was determined by immunohistochemical detection of activated caspase-3.
Treatment with EP significantly reduced mechanical and cold allodynia following spinal nerve ligation injury. TNF-α protein levels in the pre-EP (4.7 ± 1.2 pg/200 µg; P < 0.001) and post-EP (6.4 ± 1.8 pg/200 µg; P < 0.001) groups were 2-3 times lower than the control group (14.4 ± 1.2 pg/200 µg). The percentages of neurons and satellite cells that co-localized with caspase-3 were also significantly lower in the pre-EP and post-EP groups than the control group.
These results demonstrate that EP has a strong anti-allodynic effect that acts through the inhibition of TNF-α expression and apoptosis in DRG after spinal nerve ligation injury.
The Korean journal of pain 10/2012; 25(4):213-20.
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ABSTRACT: Lumbar spinal stenosis is a commonly treated with epidural injections of local anesthetics and corticosteroids, however, these therapies may relieve leg pain for weeks to months but do not influence functional status. Furthermore, the majority of patients report no substantial symptom change over the repeated treatment. Utilizing balloon catheters, we successfully treated with three patients who complained persistent symptoms despite repeated conventional steroid injections. Our results suggest that transforaminal decompression using a balloon catheter may have potential in the nonsurgical treatment of spinal stenosis by modifying the underlying pathophysiology.
The Korean journal of pain 01/2012; 25(1):55-9.
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ABSTRACT: Spinal nerve ligation (SNL) injury in rats produces a pain syndrome that includes mechanical and thermal allodynia. Previous studies have indicated that proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) play an important role in peripheral mediation of neuropathic pain, and that altered dorsal root ganglion (DRG) function and degree of DRG neuronal apoptosis are associated with spinal nerve injury. The present study was conducted to evaluate the expression of TNF-α and the extent of apoptosis in the dorsal root ganglion after SNL in rats.
Sprague-Dawley rats were subjected to SNL of the left L5 and L6 spinal nerves distal to the DRG and proximal to the formation of the sciatic nerve. At postoperative day 8, TNF-α protein levels in the L5-6 DRG were compared between SNL and naive groups using ELISA. In addition, we compared the percentage of neurons injured in the DRG using immunostaining for apoptosis and localization of activated caspase-3.
SNL injury produced significant mechanical and cold allodynia throughout the 7-day experimental period. TNF-α protein levels were increased in the DRG in rats that had undergone SNL (12.7 ± 3.2 pg/100 µg, P < 0.001) when compared with naïve rats (4.1 ± 1.4 pg/100 µg). The percentage of neurons or satellite cells co-localized with activated caspase-3 were also significantly higher in rats with SNL than in naïve rats (P < 0.001, P < 0.05, respectively).
SNL injury produces mechanical and cold allodynia, as well as TNF-α elevation and apoptosis in the DRG.
The Korean journal of pain 12/2011; 24(4):185-90.
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ABSTRACT: Facet joint disease plays a major role in axial low-back pain. Few diagnostic tests and imaging methods for identifying this condition exist. Single photon emission computed tomography (SPECT) is reported that it has a high sensitivity and specificity in diagnosing facet disease. We prospectively evaluated the use of bone scintigraphy with SPECT for the identification of patients with low back pain who would benefit from medial branch block.
SPECT was performed on 33 patients clinically suspected of facet joint disease. After SPECT, an ultrasound guided medial branch block was performed on all patients. On 28 SPECT-positive patients, medial branch block was performed based on the SPECT findings. On 5 negative patients, medial branch block was performed based on clinical findings. For one month, we evaluated the patients using the visual analogue scale (VAS) and Oswestry disability index. SigmaStat and paired t-tests were used to analyze patient data and compare results.
Of the 33 patients, the ones who showed more than 50% reduction in VAS score were assigned 'responders'. SPECT positive patients showed a better response to medial branch blocks than negative patients, but no changes in the Oswestry disability index were seen.
SPECT is a sensitive tool for the identification of facet joint disease and predicting the response to medial branch block.
The Korean journal of pain 06/2011; 24(2):81-6.
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ABSTRACT: The implantation of spinal cord stimulators (SCSs) to treat chronic intractable pain is steadily increasing. And there is an increased likelihood of instances where other therapies or procedures are found to interfere with SCS function, which in turn may result in pain. Since SCS utilize electric impulses as well as magnets, special considerations need for patients with a SCS in situ who require these procedures. The present report describes a case where radiofrequency (RF) ablation of the third occipital nerve resulted in spontaneous activation of a cervical SCS device.
Korean journal of anesthesiology 12/2010; 59 Suppl:S226-8.
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ABSTRACT: Monitoring of cardiac output is required during anesthesia for off-pump coronary artery bypass (OPCAB) surgery. Recently, FloTrac, a new device for arterial pressure waveform analysis for cardiac output (APCO) monitoring without external calibration, was developed. The authors have compared APCO with STAT-mode continuous cardiac output (SCCO) in patients undergoing OPCAB surgery.
A clinical study.
A university hospital (single institution).
Thirty consecutive patients undergoing elective OPCAB surgery.
Arterial pressure measurement with FloTrac, pulmonary arterial catheter insertion.
APCO and SCCO measurements were recorded after pulmonary artery catheter insertion (T1), after sternotomy (T2), after heart positioning for left anterior descending artery anastomosis (T3, T4), after heart positioning for obtuse marginal artery anastomosis (T5, T6), after heart positioning for posterior descending artery anastomosis (T7, T8), and after sternal closure (T9). APCO and SCCO were compared using the Bland-Altman method and the percentage error by Critchley's criteria. SCCO and APCO ranged from 2.1 to 6.9 L/min and 1.2 to 7.4 L/min, respectively, and showed low correlation (r = 0.29). The overall bias by the Bland-Altman method between SCCO and APCO was -0.23 L/min, with a precision of -1.4 to 0.9 L/min, and the overall limits of agreement were -2.5 to 2.0 L/min. The overall mean CO was 4.0 ± 0.95 L/min. The overall percentage error between SCCO and APCO measurements was 57%.
Uncalibrated APCO values do not agree with thermodilution SCCO and significantly overestimated the SCCO in patients undergoing OPCAB surgery. Further evaluation is required to verify the clinical acceptance of FloTrac APCO in OPCAB surgery.
Journal of cardiothoracic and vascular anesthesia 10/2010; 24(5):767-71. · 1.06 Impact Factor
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ABSTRACT: Persistent and intractable hiccups (with respective durations of more than 48 hours and 1 month) can result in depression, fatigue, impaired sleep, dehydration, weight loss, malnutrition, and aspiration syndromes. The conventional treatments for hiccups are either non-pharmacological, pharmacological or a nerve block treatment. Pulsed radiofrequency lesioning (PRFL) has been proposed for the modulation of the excited nervous system pathway of pain as a safe and nondestructive treatment method. As placement of the electrode in close proximity to the targeted nerve is very important for the success of PRFL, ultrasound appears to be well suited for this technique. A 74-year-old man suffering from intractable hiccups that had developed after a coronary artery bypass graft and had continued for 7 years was referred to our pain clinic. He had not been treated with conventional methods or medications. We performed PRFL of the phrenic nerve guided by ultrasound and the hiccups disappeared.
The Korean journal of pain 09/2010; 23(3):198-201.
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ABSTRACT: Neuropathic pain resulting from diverse causes is a chronic condition for which effective treatment is lacking. The goal of this study was to test whether dexamethasone exerts a preemptive analgesic effect with bupivacaine when injected perineurally in the spared nerve injury model.
Fifty rats were randomly divided into five groups. Group 1 (control) was ligated but received no drugs. Group 2 was perineurally infiltrated (tibial and common peroneal nerves) with 0.4% bupivacaine (0.2 ml) and dexamethasone (0.8 mg) 10 minutes before surgery. Group 3 was infiltrated with 0.4% bupivacaine (0.2 ml) and dexamethasone (0.8 mg) after surgery. Group 4 was infiltrated with normal saline (0.2 ml) and dexamethasone (0.8 mg) 10 minutes before surgery. Group 5 was infiltrated with only 0.4% bupivacaine (0.2 ml) before surgery. Rat paw withdrawal thresholds were measured using the von Frey hair test before surgery as a baseline measurement and on postoperative days 3, 6, 9, 12, 15, 18 and 21.
In the group injected preoperatively with dexamethasone and bupivacaine, mechanical allodynia did not develop and mechanical threshold forces were significantly different compared with other groups, especially between postoperative days 3 and 9 (P < 0.05).
In conclusion, preoperative infiltration of both dexamethasone and bupivacaine showed a significantly better analgesic effect than did infiltration of bupivacaine or dexamethasone alone in the spared nerve injury model, especially early on after surgery.
The Korean journal of pain 09/2010; 23(3):166-71.
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ABSTRACT: The pathophysiological and neurochemical changes following spinal injury are not yet elucidated. This study was designed to evaluate the morphological changes of the dorsal horn of the spinal cord and profiles of pain behaviors following intraspinal injection of NMDA in rats.
RATS WERE RANDOMIZED INTO THREE GROUPS: a sham-operated control group and groups where the rats received 10 mM or 100 mM N-methyl-D-aspatate (NMDA) injected into their spinal dorsal horn. Following injection, hypersensitivity to cold and mechanical stimuli and excessive grooming behaviors were assessed serially for four weeks. Morphological changes of the spinal cord were evaluated four weeks after intraspinal injection.
Few animals in the NMDA groups developed hypersensitivity to cold and mechanical stimuli. The number of groomers and the severity of excessive grooming were significantly higher in the 100 mM NMDA group than those values of the control and 10 mM NMDA groups. The size of the neck region (lamina III-IV) was significantly smaller in the 100 mM NMDA group than in the control and 10 mM NMDA groups.
In conclusion, intraspinal injection of NMDA in rats leads to the pathological sequela in the spinal cord and to excessive grooming behavior. These results support the use of NMDA and excessive grooming behavior after excitotoxic SCI as a model to study chronic pain after SCI.
The Korean journal of pain 06/2010; 23(2):109-15.
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ABSTRACT: Adefovir dipivoxil (ADV) is a nucleotide analogue that is known to be effective for lamivudine-resistant hepatitis B virus (HBV) mutants as well as wild-type HBV. The aim of this study is to assess the efficacy of ADV against lamivudine-resistant genotype C HBV mutants.
Thirty-five patients with breakthrough hepatitis due to lamivudine-resistant HBV received ADV 10 mg daily with discontinuation of lamivudine. Quantitative HBV DNA, HBeAg, liver function test including alanine aminotransferase (ALT) was checked every 4-12 weeks to evaluate the efficacy of ADV.
ADV was administered for a median of 48 weeks (range: 24-120 weeks). The rate of serum HBV DNA loss was 68.6%, 80.0%, 84.0%, and 88.2% at weeks 12, 24, 36, and 48, respectively. The rate of serum HBeAg seroconversion was 8.3% and 14.3% at weeks 24 and 48, respectively. The rate of serum ALT normalization at week 48 was 70.6%. Within 32 weeks after stopping ADV therapy, serum HBV DNA levels increased to a median of 378.9 pg/ml in 88.9% of patients, who were treated for a median of 40 weeks. Moreover, in some patients, the ALT level increased to more than five times the upper limit of normal.
Administration of ADV is an effective option for the treatment of patients with lamivudine-resistant genotype C HBV infection.
Liver international: official journal of the International Association for the Study of the Liver 03/2007; 27(1):47-53. · 3.82 Impact Factor
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ABSTRACT: Viral suppression of the hepatitis B virus (HBV) can be induced by lamivudine, but the relapse seen in many patients after cessation of lamivudine therapy is troublesome. We thought that the host immune response is important to prevent viral relapse. We compared the frequency of HBV-specific CD8+ T cells in the peripheral blood and their expansion capacity after exposure to viral antigen between the patients showing sustained HBeAg seroconversion after use of lamivudine and those patients without sustained response.
We analyzed HBV-specific CD8+ T cells that were isolated from the blood of 14 patients with HLA-A2 who showed lamivudine induced HBeAg seroconversion (HBV DNA < 0.5 pg/mL, and the cells were negative for HBeAg) at the end of lamivudine therapy. The purified T cells were directly stained ex vivo, after they had been stimulate with synthetic peptide, using the HBV core 18-27-specific HLA tetramer (Tc 18-27) and monoclonal antibody to CD8. The HBV viral load was quantified by the Amplicor HBV Monitor assay.
In patients with a sustained HBeAg response (the sustained group) for a duration of 15.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 49.5 (15-135). On the contrary, in patients who experienced relapse (the relapsed group) during a median of 7.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 13.5 (0-95). Especially, among patients with a viral load of HBV DNA < 1 X 10(3) copies at the end of treatment, the median number of Tc 18-27 cells out of 5 X 10(4) CD8+ T cells was 87 (45-135) in sustained group compared to 12 (6-50) in the relapsed group. All patients in the sustained group demonstrated a vigorous expansion of the core 18-27-specific CD8+ T cells after stimulation with viral peptide, in contrast to only 3 out of 8 patients in the relapsed group.
This study demonstrates that the frequency and functional responsiveness of the circulating HBV-specific CD8+ T cells may be important for obtaining a sustained HBeAg response to lamivudine.
The Korean Journal of Hepatology 03/2005; 11(1):34-42.
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ABSTRACT: It has been unclear whether immediate antiviral therapy or observation under the expectation of spontaneous inactivation of hepatitis B virus (HBV), is more appropriate for the treatment of chronic hepatitis B (CHB) with acute exacerbation. We intended to analyze the short-term natural course of CHB with acute exacerbation and evaluate the efficacy of lamivudine.
We analyzed 35 CHB patients with acute exacerbation (positive HBV DNA or HBeAg and ALT>400 IU/L) between March 2000 and May 2003. We regularly checked serum HBV DNA, HBeAg and liver function tests including ALT every 1 to 3 months. If ALT was above 100 IU/L during the follow-up period, patients were treated with 100 mg lamivudine orally once a day. We compared the efficacy of lamivudine use between this group and the group provided with immediate lamivudine trial at their first visit.
27 CHB patients with acute exacerbation were observed without immediate lamivudine trial. In 5 of these patients normal ALT, negative HBeAg and HBV DNA were maintained during 19 months (group 1a). Slightly elevated or normal ALT was maintained without HBeAg seroconversion in 3 patients (group 1b). However, serum ALT flared up above 100 IU/L in 19 patients within 5 months. So, lamivudine was tried on these patients (group 2). The serum HBV DNA was extremely low, being 6.5 pg/mL in group 1a compared to 518.1 pg/mL in group 2. Spontaneous inactivation of HBV was observed in 71.4% (5/7) of patients with HBV DNA less than 20 pg/ mL at the first visit. ALT was lower and HBV DNA was higher in group 2 than the 8 patients who received immediate lamivudine trial at the first visit (group 3). The response rate of lamivudine was similar between group 2, 56.3% (9/16) and group 3, 62.5% (5/8).
Spontaneous inactivation of HBV was expected in CHB with acute exacerbation and extremely low level of HBV DNA (less than 20 pg/mL) in a short term follow-up period. Immediate lamivudine therapy might be more appropriate in most CHB patients with acute exacerbation.
The Korean Journal of Hepatology 03/2004; 10(1):22-30.
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ABSTRACT: The generation of oxygen free radicals has been implicated in the pathogenesis of experimental pancreatitis. The aim of this study was to determine the role of oxygen free radicals in patients with acute pancreatitis.
The plasma levels of C-reactive protein (CRP), lipid peroxide (LPO), myeloperoxidase (MPO) and superoxide dismutase (SOD) were measured in 13 patients with acute pancreatitis and 14 healthy volunteers.
Among the patients with acute pancreatitis, there were higher plasma levels of LPO and MPO and lower SOD activity in patients with severe pancreatitis than in those with mild pancreatitis. However, there was no significant difference in the serum marker of oxidative stress no matter what the etiology was. The LPO level was especially correlated with the concentration of serum CRP and CT severity index.
The oxygen free radicals may be closely associated with inflammatory process and the severity of acute pancreatitis. Especially, the concentration of plasma LPO is a meaningful index for determining the severity of the disease.
World Journal of Gastroenterology 11/2003; 9(10):2266-9. · 2.47 Impact Factor
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ABSTRACT: The protective role of HBV-specific CD8+ cells is dependent on their ability to efficiently migrate to the infected liver, where they may exert an effector function. The migratory behavior of CD8+ cells is influenced by their expression of different chemokine receptors. This study was intended to analyse the pattern of chemokine receptor expression of HBV specific CD 8+ cells in chronic B viral infection.
We analysed the CCR5 and CCR3 profile of HBV-specific CD8+ cells isolated from the blood and liver of patients with different patterns of HBV infection. Purified T cells were stained directly ex vivo, or after antigen-specific stimulation, using HBV peptide-specific HLA tetramers and monoclonal antibodies to CD8, CCR5 and CCR3, with analysis by flow cytometry.
In patients with chronic hepatitis B characterised by low levels of virus (serum HBV DNA <0.5 pg/mL) and minimal liver inflammation, analysis of circulating and intrahepatic CD8+ cells demonstrated that liver infiltrating Tc18-27-specific cells were preferentially CCR5+ (up to 80% of HBV-specific CD8+ cells), in contrast to cells of the same specificity within the circulating compartment (up to 35% of HBV-specific CD8+ cells). Furthermore, CCR3 was expressed by about 10% of Tc18-27+ cells infiltrating the liver, but was absent from circulating cells. Following HBV-specific stimulation in vitro the CCR5 expression of circulating Tc18-27-specific cells was up-regulated, to levels found in liver infiltrating cells, whereas CCR3 expression was unchanged.
The chemokine receptor profile of HBV-specific CD8+ cells is influenced by the anatomical site of these cells, and the clinical pattern of disease. The ability of circulating HBV-specific CD8+ cells of patients with low replicating virus to upregulate CCR5 suggests that these cells may respond to increases in virus replication by efficiently migrating into the infected liver.
Taehan Kan Hakhoe chi = The Korean journal of hepatology 12/2002; 8(4):363-70.
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ABSTRACT: Hepatitis B virus(HBV) specific cytotoxic T lymphocyte (CTL) response is believed to play a major role in virus control and liver damage in chronic hepatitis B(CHB). We performed this study to evaluate whether HBV specific CTL could be visualized directly by tetrameric HLA-A2/core 18-27 complex(T c18-27) in the peripheral blood and liver of patients with CHB. On the basis of our results we clarified patients intrahepatic compartmentalization and correlation with HBV specific CTL and viral replication or liver damage.
We stained peripheral blood mononuclear cells of 33 HLA-A2 + and 8 HLA-A2 patients with CHB with cytochrome conjugated anti-CD8 mAb and phycoerythrin conjugated T c18-27. Among these we analysed intrahepatic lymphocyte of 11 HLA-A2 + patients. We compared the frequency of T c18-27 specific CD8+ cells with serum HBV-DNA levels or alanine aminotransferase(ALT) levels.
The frequency of circulating T c18-27 specific CD8+ cell was higher(9-101 cells per 50,000 CD8+ cells) than background level in 14 among 33 patients. The frequency of intrahepatic T c18-27 specific CD8+ cells was 12-2100 cells per 50,000 CD8+ cells in 8 out of 11 patients whose liver was obtained This was 17.4-150 times higher than circulating T c18-27 specific CD8+ cells. The frequency of circulating T c18-27 specific CD8+ cells was increased in 10 out of 18 patients with serum HBV DNA level <0.5 pg/mL and ALT < 40 IU/L. It was increased in just 4 out of 15 patients with HBV DNA level > 800 pg/mL and ALT > 70 IU/L. The frequency of intrahepatic T c18-27 CTL tended to be lower in high levels of serum HBV DNA and was not correlated with liver inflammation.
This study proves that if HBV-specific CTLs are barely detectable in the peripheral blood of CHB, much more HBV-specific CTLs are in the liver and most HBV-specific CTLs are infiltrated in the liver. Also, in the presence of an effective HBV specific CD8 response the inhibition of viral replication can be independent of liver damage.
Taehan Kan Hakhoe chi = The Korean journal of hepatology 06/2002; 8(2):139-48.
