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ABSTRACT: : The presence/absence of extracapsular invasion in metastatic lymph nodes has been reported as being significantly correlated with the prognosis in a wide variety of cancers. However, the influence of extracapsular invasion in the metastatic lymph nodes on the prognosis in patients with stage III rectal cancer has not yet been investigated.
: We investigated the presence/absence of extracapsular invasion in the metastatic nodes of the relevant main/lateral lymph node group in patients with rectal cancer to determine the usefulness of this parameter for stratifying the prognosis of patients with stage III rectal cancer.
: This was a single-institution study.
: This study was conducted at a single institution.
: We enrolled 101 consecutive patients with stage III rectal cancer who had undergone curative surgery with extended lymph node dissection and investigated the presence/absence of extracapsular invasion in the regional metastatic lymph nodes to determine the usefulness of such stratification for a more precise prediction of the patient prognosis.
: The main outcomes measured were the disease-free and overall survival rates.
: Univariate analysis revealed a significantly poorer prognosis, in terms of both the disease-free survival rate (p = 0.003) and overall survival rate (p = 0.008), of the pN3-extracapsular invasion-positive cases in comparison with the pN3-extracapsular invasion-negative cases. Multivariate analysis revealed the presence/absence of extracapsular invasion in the metastatic lymph nodes as the only variable that was statistically significantly associated with the disease-free survival rate (p = 0.011).
: This was a retrospective study in a small number of patients from a single institution. There were no comparator groups.
: Detailed stratification of pN3 cases based on the presence/absence of extracapsular invasion in metastatic lymph nodes has the potential to contribute significantly to more available prediction of the prognosis of patients with stage III colorectal cancer.
Diseases of the Colon & Rectum 06/2013; 56(6):726-32. · 3.13 Impact Factor
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ABSTRACT: OBJECTIVE:: To investigate the incidence of BT in the mesenteric lymph node and bacteremia after an esophagectomy using a bacterium-specific ribosomal RNA-targeted reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR). BACKGROUND:: There is little evidence regarding the occurrence of bacterial translocation (BT) and its correlation to postoperative infectious complications after an esophagectomy. METHODS:: Eighteen patients with esophageal cancer were studied. Mesenteric lymph nodes were harvested from the jejunal mesentery before surgical mobilization (MLN-1) and after the restoration of bowel continuity (MLN-2). Blood and sputum were also sampled before surgery (Blood-1 and Sputum-1) and on postoperative day 1 (Blood-2 and Sputum-2). RESULTS:: The detection rates of bacteria in the MLN-2 (56%) and Blood-2 (56%) were significantly higher than those in the MLN-1 (17%) and Blood-1 (22%), indicating that surgical stress induces BT. The detection rate was not different between Sputum-1 (80%) and Sputum-2 (78%). There was an 80% sequence homology between the RT-qPCR products in the MLN-2 and Blood-2, whereas the homology was only 20% between Blood-2 and Sputum-2. In the patients with positive bacteria in the MLN-2 sample, there was a greater incidence of postoperative infectious complications than in patients without bacteria in the MLN-2 sample (P = 0.04). The postoperative hospital stay was also longer (P = 0.037) for patients with positive bacteria in the MLN-2 sample. CONCLUSIONS:: BT frequently occurs during esophagectomies, and postoperative bacteremia is likely to be gut-derived. Patients with positive bacteria in the MLN-2 sample should be carefully managed because these patients are more susceptible to postoperative infectious complications.
Annals of surgery 04/2013; · 7.90 Impact Factor
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ABSTRACT: A 69-year-old man with jaundice was diagnosed with cancer of the ampulla of Vater by endoscopic retrograde cholangiopancreatography and abdominal computed tomography. A screening gastrointestinal endoscopy showed middle thoracic esophageal cancer and early gastric cancer on the anterior wall of the lower gastric body. We chose a two-stage operation for synchronous triple primary cancer of the esophagus, stomach, and ampulla of Vater, in order to safely perform the curative resection of these three cancers. The first-stage operation consisted of a right transthoracic subtotal esophagectomy with mediastinal and cervical lymph node dissection, an external esophagostomy in the neck, and a gastrostomy. Thirty-five days after the first surgery, a total gastrectomy with regional lymph node dissection, and a pancreatoduodenectomy with Child's reconstruction were performed as the second-stage surgery. Esophageal reconstruction was achieved using the ileocolon via the percutaneous route without vascular anastomosis.
Surgery Today 03/2013; · 1.22 Impact Factor
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Koji Komori,
Yukihide Kanemitsu,
Kenya Kimura,
Norifumi Hattori,
Tsuyoshi Sano,
Seiji Ito, Tetsuya Abe,
Yoshiki Senda,
Kazunari Misawa,
Yuichi Ito,
Norihisa Uemura,
Yasuhiro Shimizu
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ABSTRACT: Aim: To examine the usefulness of the histopathological finding of tumor necrosis for stratifying TNM stage IV colorectal cancer in R0 status. PATIENTS AND METHODS: We enrolled 98 patients with stage IV colorectal cancer, without residual disease after resection. The extent of necrosis was assessed using published thresholds, the extent was graded as "absent", "moderate" (<30% of tumor area), or "severe" (≥30%) in each section. RESULTS: In multivariate analysis, the only significant difference in the disease-free survival rate was related to tumor necrosis (p=0.01) and the significant differences in the overall survival rates were related to the maximum tumor size and the degree of tumor necrosis (p=0.02 and p=0.001, respectively). CONCLUSION: Tumor necrosis is associated with a poor prognosis in colorectal cancer and may allow the stratification of TNM stage IV patients without residual disease after surgery.
Anticancer research 03/2013; 33(3):1099-1105. · 1.73 Impact Factor
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Koji Komori,
Yukihide Kanemitsu,
Kenya Kimura,
Kazunori Yawata,
Yasuhiro Shimizu,
Tsuyoshi Sano,
Seiji Ito, Tetsuya Abe,
Yoshiki Senda,
Kazunari Misawa,
Yuichi Ito,
Norihisa Uemura,
Tomoyuki Kato
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ABSTRACT: Backgroun /Aims: There have been numerous studies on surgical procedures for familial adenomatous polyposis (FAP), but the evolution in surgical treatments as they pertain to the major perioperative item, i.e., complications, as well as advantages and disadvantages of surgery, in only one institution have not been reported. We examined this surgical treatment evolution in FAP patients. Methodology: We enrolled 67 FAP patients who had undergone surgery and classified them into three groups, i.e., early phase (1965 to 1977), intermediate phase (1978 to 1987), and late phase (1988 to 2004). We assessed clinicopathological findings and outcomes in these three groups.Results: With the passage of time, surgical techniques and therapeutic benefits improved, but the overall survival rates of early and late phase patients were significantly better than that of intermediate phase patients.Conclusion: As the surgical techniques improved, patient stress diminished but outcomes in the late period were not always better than in the early period. Surveillance has been enhanced by the increased prevalence of colonoscopy and genetic research has also contributed to better disease management. It is necessary to research the prognosis of FAP patients in the future.
Hepato-gastroenterology 01/2013; 60(125). · 0.66 Impact Factor
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Koji Komori,
Yukihide Kanemitsu,
Seiji Ishiguro,
Yasuhiro Shimizu,
Tsuyoshi Sano,
Seiji Ito, Tetsuya Abe,
Yoshiki Senda,
Kazunari Misawa,
Yuichi Ito,
Norihisa Uemura,
Tomoyuki Kato
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ABSTRACT: Previous studies have not identified how to determine the optimal distal margin in rectal cancer based on histopathological diagnosis. We examined the surgical distal resection margin from a histopathological viewpoint.
We enrolled 629 patients. The type of distal spread was evaluated, and the maximum length of distal spread was measured using a micrometer.
The frequencies of discontinuous spread type were 1.0%, 8.4%, 52.9%, and 81.5%, and the average lengths of distal spread were .5 ± 1.3 mm, 7 ± 1.8 mm, 2.7 ± 2.4 mm, and 10.0 ± 9.5 mm for well-differentiated adenocarcinomas, moderately differentiated adenocarcinomas, solid (por1)-type poorly differentiated adenocarcinomas, and nonsolid (por2)-type poorly differentiated adenocarcinomas, (moderately vs solid [por1] type: P = .004), respectively.
The surgical distal resection margin based on pathological diagnosis is longer somewhat than that based on macroscopic findings. Therefore, it is important to select surgical procedures with great care to ensure an adequate surgical distal resection margin.
American journal of surgery 05/2012; 204(4):474-80. · 2.36 Impact Factor
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Koji Komori,
Yukihide Kanemitsu,
Seiji Ishiguro,
Yasuhiro Shimizu,
Tsuyoshi Sano,
Seiji Ito, Tetsuya Abe,
Yoshiki Senda,
Kazunari Misawa,
Yuichi Ito,
Norihisa Uemura,
Tomoyuki Kato
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ABSTRACT: We aimed to clarify the clinicopathological features of poorly differentiated colorectal adenocarcinomas and to define two subtypes of these adenocarcinomas.
We enrolled 78 patients, who had undergone surgery for poorly differentiated colorectal adenocarcinoma. On the basis of the microscopy results, the Por1 type is characterized by cancer cells with solid growth and little stroma; most cells contained round-shaped nuclei. The Por2 type is characterized by cancer cells with a predominantly trabecular structure; these tumors are rich in fibrous stroma. The two groups were compared for clinicopathological factors.
The frequency of metastasis of the lymph node, liver, lung, and peritoneum in the Por2 group was significantly higher than that in the Por1 group. The survival rate in the Por2 group was lower than that in the Por1 group.
The classification system described in this study is a simple and easy method for predicting poorly differentiated colorectal adenocarcinomas, and the prognosis of patients with Por2 tended to be unfavorable than that of Por1.
Anticancer research 10/2011; 31(10):3463-7. · 1.73 Impact Factor
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ABSTRACT: Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) is a key mediator of long-term potentiation (LTP), which can be triggered by N-methyl-d-aspartate (NMDA) receptor-mediated Ca(2+) influx. We previously demonstrated that Fyn kinase-mediated phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 in the dorsal horn was involved in a neuropathic pain state even 1 week after nerve injury. Here we show that Y1472F-KI mice with a knock-in mutation of the Tyr1472 site to phenylalanine did not exhibit neuropathic pain induced by L5 spinal nerve transection, whereas they did retain normal nociceptive responses and induction of inflammatory pain. Phosphorylation of NR2B at Tyr1472 was only impaired in the spinal cord of Y1472F-KI mice among the major phosphorylation sites. There was no difference in the Ca(2+) response to glutamate and sensitivity to NMDA receptor antagonists between naive wild-type and Y1472F-KI mice, and the Ca(2+) response to glutamate was attenuated in the Y1472F-KI mice after nerve injury. Autophosphorylation of CaMKII at Thr286 was markedly impaired in Y1472F-KI mice after nerve injury, but there was no difference in phosphorylation of CaMKII at Thr305 or protein kinase Cγ at Thr674, and activation of neuronal nitric oxide synthase and microglia in the superficial layer of spinal cord between wild-type and Y1472F-KI mice after the operation. These results demonstrate that the attenuation of neuropathic pain is caused by the impaired NMDA receptor-mediated CaMKII signaling in Y1472F-KI mice, and suggest that autophosphorylation of CaMKII at Thr286 plays a central part not only in LTP, but also in persistent neuropathic pain.
European Journal of Neuroscience 09/2010; 32(5):798-810. · 3.63 Impact Factor
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ABSTRACT: The increasing number of patients with chronic pain in Japan has become a major issue in terms of the patient's quality of life, medical costs, and related social problems. Pain is a multi-dimensional experience with physiological, affective, cognitive, behavioral and social components, and recommended to be managed via a combination of bio-psycho-social aspects. However, a biomedical approach is still the dominant method of pain treatment in Japan. The current study aimed to evaluate comprehensive psychological functions and processes in Japanese chronic pain patients.
The Rorschach Comprehensive System was administered to 49 in-patients with non-malignant chronic pain. Major variables and frequencies from the test were then compared to normative data from non-patient Japanese adults by way of the t-test and chi-square test.
Patients exhibited high levels of emotional distress with a sense of helplessness with regard to situational stress, confusion, and ambivalent feelings. These emotions were managed by the patients in an inappropriate manner. Cognitive functions resulted in moderate dysfunction in all stages. Information processing tended to focus upon minute features in an inflexible manner. Mediational dysfunction was likely to occur with unstable affective conditions. Ideation was marked by pessimistic and less effective thinking. Since patients exhibited negative self-perception, their interpersonal relationship skills tended to be ineffective. Originally, our patients displayed average psychological resources for control, stress tolerance, and social skills for interpersonal relationships. However, patient coping styles were either situation- or emotion-dependent, and patients were more likely to exhibit emotional instability influenced by external stimuli, resulting in increased vulnerability to pain.
Data gathered from the Rorschach test suggested psychological approaches to support chronic pain patients that are likely to be highly beneficial, and we thus recommend their incorporation into the course of current pain treatments.
BioPsychoSocial Medicine 01/2010; 4:20.
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ABSTRACT: Functional somatic syndrome (FSS) with abdominal pain include functional gastrointestinal disorder, chronic pancreatitis, chronic pelvic pain syndrome, which generally contain autonomic dysfunction. Regarding the treatment of FSS, it is important to know about FSS for a therapist at first. Secondly, the therapist should find out physical dysfunction of patients positively, and confirm objectively the hypotheses about both peripheral and central pathophysiological mechanisms as much as possible. Heart rate variability is an easy method, and useful to assess autonomic function. After grasping the patient's explanatory model about the illness, the therapist showes the most acceptable treatment for the patient at last.
Nippon rinsho. Japanese journal of clinical medicine 09/2009; 67(9):1773-7.
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ABSTRACT: Pancreatic gastrinoma is a rare non-beta islet cell tumor. Approximately 60% of gastrinomas are malignant; despite the fact that they are usually slow growing, liver metastases have a major impact on prognosis. Most authors have advocated aggressive surgical management as being the only potentially curative therapy to improve survival as well as to provide outstanding relief from symptoms. We present a case of a 57-year-old man referred to our hospital with a diagnosis of liver metastases from pancreatic gastrinoma, with suspected involvement of the inferior vena cava (IVC). At the age of 37 years, he was diagnosed in his local hospital as having a pancreatic gastrinoma, with liver metastases, and he underwent distal pancreatectomy, splenectomy and enucleation of liver metastases. A liver tumor recurred twice, 7 and 9 years after the first surgery, for which double liver resections were performed: the first time he underwent enucleation of multiple liver metastases in segments II, III, IV, V, VI, VII and VIII, with resection of the right hepatic vein and partially resection of the diaphragm; the second time he underwent enucleation of multiple liver metastases in segments II, III, IV, and V. In our hospital, 8 years after the last surgery, the patient underwent right extended trisectionectomy, resection of segment I, combined resection of the IVC, and partial removal of the diaphragm. To the best of our knowledge, from a review of the literature, this is the first case to achieve successful long-term survival through aggressive surgical management of this type of metastatic endocrine tumor. The patient described here is still alive, free of disease and leading a normal life, 20 years after the initial diagnosis and 3 years after the last surgery.
Journal of Hepato-Biliary-Pancreatic Surgery 04/2009; 16(5):692-8. · 1.60 Impact Factor
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ABSTRACT: This report presents a case of a left hepatectomy and a caudate lobectomy combined resection of the ventral segment of the right anterior sector for hilar cholangiocarcinoma using percutaneous transhepatic portal vein embolization (PVE). The patient was a 44-year-old man admitted to a local hospital with obstructive jaundice. He was diagnosed to have hilar cholangiocarcinoma and was referred to the hospital for further treatment. Cholangiography revealed stenosis of the left hepatic duct and the hilar bile ducts. The dorsal branch of the right anterior sector joined the right posterior branch and the tumor did not invade to the confluence of these branches. Arteriography and portography reconstructed by multidetector-raw computed tomography revealed the ventral branches of the right anterior sector, which separately diverged from the other right anterior branches. It was therefore necessary to perform a left hepatectomy and caudate lobectomy combined resection of the ventral segment of the right anterior sector to completely remove the tumor. Portal vein embolization was thus performed on the left portal vein and the ventral branches of the right anterior sector. Intraoperatively, when the hepatic artery was temporally clamped, the demarcation between the ventral segment and the dorsal segment of the right anterior sector could be clearly visualized. The planned surgery was performed safely. This case demonstrates that the utilization of PVE is useful for a difficult and intricate hepatectomy, which requires an accurate identification of a hepatic subsegment.
Surgery Today 02/2009; 39(7):628-32. · 1.22 Impact Factor
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Pancreas 08/2008; 37(1):104-7. · 2.39 Impact Factor
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ABSTRACT: Although studies indicate that patient sex modulates the process of hepatic regeneration, it remains unknown whether sex has a role in the outcome of preoperative right portal vein embolization (PVE). We analyzed the effects of patient sex on the outcome of right PVE followed by major hepatectomy.
Retrospective study.
Academic research.
Eighty-eight patients (42 men and 46 women) who underwent preoperative right PVE for bile duct carcinoma were analyzed retrospectively.
The percentage liver volume change, the plasma indocyanine green clearance rate, and the rate of postoperative hepatic failure were compared between men and women.
The mean (SD) volume of the nonembolized lobe after PVE in women (323 [61] mL/m(2)) was statistically significantly greater than that in men (287 [61] mL/m(2)) (P =.008). The mean (SD) ratio of the nonembolized lobe to the total liver volume was also statistically significantly greater in women (45.8% [5.8%]) than in men (42.0% [5.9%]) (P =.003). The mean (SD) indocyanine green clearance rate of the future liver remnant was 0.075 [0.014] in women and 0.056 [0.011] in men (P =.001). The incidence of postoperative hepatic failure was higher in men (12 of 42 [28.6%]) than in women (8 of 46 [17.4%]) (P =.16).
These results indicate that sex dimorphism can be present in the outcome of preoperative right PVE.
Archives of surgery (Chicago, Ill.: 1960) 04/2008; 143(3):254-9; discussion 259. · 4.32 Impact Factor
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ABSTRACT: Gallbladder cancer is a disease with poor prognosis, especially when it is associated with distant metastasis. Here we report a rare case of a patient with gallbladder cancer with extensive local and distant lymph node metastases and multiple liver metastases who has survived for more than 13 years through aggressive treatments. A 54-year-old woman developed right upper quadrant pain. Computed tomography (CT) revealed a papillary tumor in the gallbladder. Low-density tumors in segments 4, 5, and 8 of the liver and extensive paraaortic lymph node swelling were observed. She underwent central hepatic bisectionectomy and paraaortic lymphadenectomy. Two months later, hepatic metastases were found in segments 2, 3, 6, and 7, and percutaneous ethanol injection and transcatheter arterial chemoembolization were performed. Twelve months after the first surgery, CT revealed lymph node swelling around the right external iliac artery and behind the left renal vein. Metastatic lymph node dissection and resection and reconstruction of the right external iliac artery and vein with artificial graft replacements were performed. Two months later, CT revealed a paraesophageal lymph node swelling, which was treated by radiotherapy. At present, 13 years after the first surgery, and 11 years after the last radiotherapy, she is alive without any sign of recurrence.
Journal of Hepato-Biliary-Pancreatic Surgery 02/2008; 15(6):648-51. · 1.60 Impact Factor
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ABSTRACT: We analyzed the clinical characteristics and patterns of recurrence of intraductal papillary mucinous neoplasms (IPMNs) from 100 consecutive surgical cases.
The average age was 62 +/- 12 years. The tumor was located in the head in 65 patients, body in 25 patients, and tail in 10 patients. Sixty-seven patients had benign IPMNs, and 33 patients had malignant IPMNs. Malignant IPMNs were observed more frequently in the head (42%) as compared with the body (20%) or tail (10%) (P < .05). During the follow-up period, 5 patients recurred and underwent second operation. In the first operation, 1 patient underwent pancreatoduodenectomy for the head tumor and the other 4 patients underwent distal pancreatectomy for the body and/or tail tumor.
Although histopathologic findings in the first operation were adenoma in 2 and carcinoma in 3 patients, all patients developed carcinoma by the time of the second operation. No hyperplasia developed recurrence. The overall recurrence rate for the head tumors was 1.5% (1 out of 65), whereas that for the body and tail tumors was 11.4% (4 out of 35) (P < .05). Metachronous multicentric recurrence was suspected in 4 cases.
These results indicate that adenomatous or carcinomatous IPMNs, especially originated from the body or tail, should be carefully observed even with a histologically negative surgical margin.
Surgery 08/2007; 142(2):136-42. · 3.10 Impact Factor
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Shinji Matsumura, Tetsuya Abe,
Tamaki Mabuchi,
Tayo Katano,
Kunio Takagi,
Emiko Okuda-Ashitaka,
Shinichi Tatsumi,
Yoshihide Nakai,
Hiroyoshi Hidaka,
Masaaki Suzuki,
Yasuharu Sasaki,
Toshiaki Minami,
Seiji Ito
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ABSTRACT: Prostaglandin E2 (PGE2), the principal pro-inflammatory prostanoid, is known to play versatile roles in pain transmission via four PGE receptor subtypes, EP1-EP4. We recently demonstrated that continuous production of nitric oxide (NO) by neuronal NO synthase (nNOS) following phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS) and NMDA receptor NR2B subunits is essential for neuropathic pain. These phosphorylation and nNOS activity visualized by NADPH-diaphorase histochemistry were blocked by indomethacin, a PG synthesis inhibitor. To clarify the interaction between cyclooxygenase and nNOS pathways in the spinal cord, we examined the effect of EP subtype-selective agonists on NO production. NO formation was stimulated in the spinal superficial layer by EP1, EP3, and EP4 agonists. While the EP1- and the EP4-stimulated NO formation was markedly blocked by MK-801, an NMDA receptor antagonist, the EP3-stimulated one was completely inhibited by H-1152, a Rho-kinase inhibitor. Phosphorylation of MARCKS and NADPH-diaphorase activity stimulated by the EP3 agonist were also blocked by H-1152. These results suggest that PGE2 stimulates NO formation by Rho-kinase via EP3, a mechanism(s) different from EP1 and EP4.
Biochemical and Biophysical Research Communications 01/2006; 338(1):550-7. · 2.48 Impact Factor
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Tetsuya Abe,
Shinji Matsumura,
Tayo Katano,
Tamaki Mabuchi,
Kunio Takagi,
Li Xu,
Akitsugu Yamamoto,
Kotaro Hattori,
Takeshi Yagi,
Masahiko Watanabe,
Takanobu Nakazawa,
Tadashi Yamamoto,
Masayoshi Mishina,
Yoshihide Nakai,
Seiji Ito
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ABSTRACT: Despite abundant evidence implicating the importance of N-methyl-D-aspartate (NMDA) receptors in the spinal cord for pain transmission, the signal transduction coupled to NMDA receptor activation is largely unknown for the neuropathic pain state that lasts over periods of weeks. To address this, we prepared mice with neuropathic pain by transection of spinal nerve L5. Wild-type, NR2A-deficient, and NR2D-deficient mice developed neuropathic pain; in addition, phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 was observed in the superficial dorsal horn of the spinal cord 1 week after nerve injury. Neuropathic pain and NR2B phosphorylation at Tyr1472 were attenuated by the NR2B-selective antagonist CP-101,606 and disappeared in mice lacking Fyn kinase, a Src-family tyrosine kinase. Concomitant with the NR2B phosphorylation, an increase in neuronal nitric oxide synthase activity was visualized in the superficial dorsal horn of neuropathic pain mice by NADPH diaphorase histochemistry. Electron microscopy showed that the phosphorylated NR2B was localized at the postsynaptic density in the spinal cord of mice with neuropathic pain. Indomethacin, an inhibitor of prostaglandin (PG) synthesis, and PGE receptor subtype EP1-selective antagonist reduced the NR2B phosphorylation in these mice. Conversely, EP1-selective agonist stimulated Fyn kinase-dependent nitric oxide formation in the spinal cord. The present study demonstrates that Tyr1472 phosphorylation of NR2B subunits by Fyn kinase may have dual roles in the retention of NMDA receptors in the postsynaptic density and in activation of nitric oxide synthase, and suggests that PGE2 is involved in the maintenance of neuropathic pain via the EP1 subtype.
European Journal of Neuroscience 10/2005; 22(6):1445-54. · 3.63 Impact Factor
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ABSTRACT: Neuropathic pain arising from peripheral nerve injury is a clinical disorder characterized by a combination of spontaneous pain, hyperalgesia and tactile pain (allodynia), and remains a significant clinical problem since it is often poorly relieved by conventional analgesics. To seek an analgesic compound(s) in Chinese herbs, we examined the effect of seven Chinese herbs that are routinely prescribed for pain management in two neuropathic pain models: allodynia induced by intrathecal administration of prostaglandin F2alpha (PGF2alpha) and by selective L5 spinal nerve transection. The extracts of Moutan cortex and Coicis semen dose-dependently alleviated the PGF2alpha-induced allodynia by oral administration 1 h before intrathecal injection of PGF2alpha. When orally administrated every day for 7 days, these extracts attenuated neuropathic pain in the ipsilateral side, but not in the contralateral side, day 7 after L5 spinal nerve transection. The increase in NADPH diaphorase activity in the spinal cord associated with neuropathic pain was also blocked by these extracts. These results suggest that Moutan cortex and Coicis semen contain substances effective in neuropathic pain.
Neuroscience Letters 12/2004; 370(2-3):130-4. · 2.11 Impact Factor
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ABSTRACT: Extrahepatic cholestasis often evokes liver injury with hepatocyte apoptosis, aberrant cytokine production, and-most importantly-postoperative septic complications. To clarify the involvement of aberrant cytokine production and hepatocyte apoptosis in impaired resistance to bacterial infection in obstructive cholestasis, C57BL/6 mice or Fas-mutated lpr mice were inoculated intraperitoneally with 10(7) colony-forming units of Escherichia coli 5 days after bile duct ligation (BDL) or sham celiotomy. Cytokine levels in sera, liver, and immune cells were assessed via enzyme-linked immunosorbent assay or real-time reverse-transcriptase polymerase chain reaction. BDL mice showed delayed clearance of E. coli in peritoneal cavity, liver, and spleen. Significantly higher levels of serum interleukin (IL) 10 with lower levels of IL-12p40 were observed in BDL mice following E. coli infection. Interferon gamma production from liver lymphocytes in BDL mice was not increased after E. coli infection either at the transcriptional or protein level. Kupffer cells from BDL mice produced low levels of IL-12p40 and high levels of IL-10 in vitro in response to lipopolysaccharide derived from E. coli. In vivo administration of anti-IL-10 monoclonal antibody ameliorated the course of E. coli infection in BDL mice. Furthermore, BDL-lpr mice did not exhibit impairment in E. coli killing in association with little hepatic injury and a small amount of IL-10 production. In conclusion, increased IL-10 and reciprocally suppressed IL-12 production by Kupffer cells are responsible for deteriorated resistance to bacterial infection in BDL mice. Fas-mediated hepatocyte apoptosis in cholestasis may be involved in the predominant IL-10 production by Kupffer cells.
Hepatology 09/2004; 40(2):414-23. · 11.66 Impact Factor
