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Anna Tani,1 Toshiyuki Yasui,2 Sumika Matsui,1 Takeshi Kato,1 Naoko Tsuchiya,3 Mitsutoshi Yuzurihara,3 Yoshio Kase,3 Minoru Irahara11Department of Obstetrics and Gynecology, 2Department of Reproductive Technology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan; 3Pharmacology Research Department, Tsumura Central Research Institute, Ibaraki, JapanPurpose: The aim of the study reported here was to determine the effect of surgical menopause by bilateral salpingo-oophorectomy (BSO) on circulating levels of cytokines and chemokines related to the pathogenesis of atherosclerosis.Patients and methods: A total of 110 women were recruited for this study from the outpatient clinic of our facility. We divided the women into three groups: 1) women with a regular menstrual cycle, 2) women in whom less than 5 years had passed since their BSO, and 3) women in whom 5 years or more had passed since their BSO. Concentrations of nine cytokines and chemokines in serum were measured.Results: The serum monocyte chemoattractant protein-1 (MCP-1) level in women in whom less than 5 years had passed since their BSO was significantly higher than in women with a regular menstrual cycle (P

Summary We investigated the effect of Ninjin-yoei-to (Ren-Shen-Yang-Rong-Tang), a Japanese herbal medicine, and found that 1000 mg/kg p.o. improved the scopolamine-induced impairment of passive avoidance response in mice. Further, the [...]

Summary Effects of saiboku-to, a traditional oriental herbal medicine, on diazepam-induced changes in cerebral acetyicholine (ACh) were investigated in rat striatum and hippocampus. Diazepam (10 mg/kg, i.p.) increased tissue concentrations [...]

Intraduodenal saiboku-to (250-1000 mg/kg) dose-dependently reduced gastric acid secretion and histamine output, without altering acetylcholine output in pylorus-ligated rats. Saiboku-to also inhibited subcutaneous bethanechol (1 mg/kg) and tetragastrin (0.3 mg/kg) -induced increases in gastric acid secretion in vagotomized pylorus-ligated rats; however, it did not inhibit subcutaneous histamine (20 mg/kg) -induced increase in acid secretion. These results, taken together, suggest a possibility that saiboku-to may inhibit histamine release. Thus, the effect of saiboku-to on histamine release was directly investigated by using anti-dinitrophenyl IgE-sensitized rat peritoneal mast cells. Antigen (dinitrophenyl)-induced histamine release from the mast cells was clearly dose-dependently inhibited by saiboku-to at concentrations of 0.1-1.0 mg/ml. These results suggest that the inhibited gastric acid secretion with saiboku-to is due to inhibited histamine release. [ABSTRACT FROM AUTHOR]

Background: This study correlated the relationship between postoperative C6 nerve root palsies and various patient-related clinical, radiographic, and surgical parameters., Methods: The medical records of 318 patients undergoing double-door cervical laminoplasty for myelopathy were reviewed. Twelve (3.8%) had postoperative C6 nerve root palsies. Their clinical, radiographic, and surgical procedures were analyzed looking for a correlation/explanation for these new C6 root deficits., Results: The following factors correlated with patients' developing new postoperative C6 nerve root deficit following double-door cervical laminoplasty; a high correlation with additional C5 palsies, narrower C6 intervertebral foraminal widths, greater anterior protrusions of the C6 articular process, and larger posterior shifts of the spinal cord on magnetic resonance (MR) between the C4/C5-C6/C7 levels., Conclusion: Factors correlating with the new onset of C6 nerve root palsies following double-door cervical laminoplasty included; a high correlation with new C5 palsies, more severe foraminal stenosis, greater anterior protrusions of the C6 articular process, and more extensive dorsal spinal cord migration., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

Aim: To analyze the clinical characteristics of thoracic ossified ligamentum flavum (OLF) and clarify prognostic factors., Material and Methods: We retrospectively collected clinical data from the medical records of 29 patients who underwent decompressive surgery for myelopathy caused by thoracic OLF from 2011 to 2019. Associations between various clinical and radiological factors and surgical outcomes were analyzed., Results: The mean preoperative and final follow-up modified Japanese Orthopaedic Association scores were 6.7 and 7.9 points, respectively (mean follow-up period, 22.4 months; P 0.0001). Univariate analysis revealed that preoperative symptom duration and postoperative epidural hematoma on magnetic resonance imaging (MRI) were significant surgical outcome predictors. The recovery rate was higher in patients without postoperative epidural hematoma (n = 16) than in those with postoperative epidural hematoma (n = 13; 38.7% ± 28.1% vs. 12.9% ± 24.4% mm; P = 0.01). Multiple regression analysis showed that postoperative epidural hematoma on MRI was a significant surgical outcome predictor (P 0.05)., Conclusion: Posterior decompressive laminectomy and resection of OLF can be considered effective. Postoperative epidural hematoma on MRI may be an important surgical outcome predictor.

Background: Normal pressure hydrocephalus (NPH) associated with tumors of the cauda equina is rare. Here, we report two cases of NPH attributed to cauda equina ependymomas., Case Description: A 63-year-old male presented with progressive gait disturbance, dementia, and urinary incontinence. When the lumbar MR documented an intradural tumor involving the cauda equina at the L2-L3 level; the tumor was excised; pathologically, it proved to be a myxopapillary ependymoma. Postoperatively, however, the patient's continued gait disturbance led to a brain CT that documented ventricular dilation consistent with NPH; following ventriculoperitoneal (VP) shunt placement his symptoms improved. A 65-year-old female also presented with gait disturbance, dementia, and urinary retention. Here, procedures were performed in reverse. When a brain CT showed hydrocephalus, a VP shunt was placed. When symptoms persisted, a lumbar MR demonstrated a T12-L2 intradural tumor; following a lumbar laminectomy for tumor excision, symptoms stabilized. The pathological diagnosis was also consistent with a conus/cauda equina ependymoma. Over the next 10 years, the patient had residual bladder dysfunction (e.g., requiring straight catheterization), but had no shunt dysfunction., Conclusion: We observed two cases of ependymomas of the cauda equina and brain CTs documenting NPH that was successfully surgically managed with stabilization of neurological deficit. In the first case, L2-L3 laminectomy for tumor removal was succeeded by shunting for NPH, while in the second case, initial VP shunting for NPH was followed by a T12-L2 laminectomy for tumor excision., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

Aim: To determine the prevalence of a deep vein thrombosis (DVT) in osteoporotic vertebral fractures., Material and Methods: Data were retrospectively collected from the medical records of 50 patients who were admitted to the Kameda Medical Center for osteoporotic vertebral fracture from 2019 to 2020. Inpatients were screened for DVT using D-dimer, and those who were screened positive underwent lower extremity venous ultrasonography to confirm DVT. Associations between various clinical factors and DVT were analyzed., Results: Six (12.0%) inpatients with osteoporotic vertebral fractures were found to have DVT. Two (33.3%) of the six had proximal DVT, although no pulmonary embolism was detected by chest computed tomography angiography. Univariate analysis showed that D-dimer values and duration from onset to hospitalization were predictive of DVT (p < 0.05)., Conclusion: The prevalence of DVT among inpatients with osteoporotic vertebral fractures was 12.0%. This finding emphasizes the importance of DVT screening using D-dimer in those with osteoporotic vertebral fractures.

Tumoral calcinosis involving the spine is rare. The involvement of the thoracic spine is rarer than that of the cervical or lumbar spine. We report a case of thoracic tumoral calcinosis accompanied by vertebral fracture with increased concentrations of inflammatory markers and no abnormalities in serum calcinosis and phosphorus concentration. A 60-year-old woman presented with complete paraplegia. Her white blood cell count and C-reactive protein (CRP) concentration were elevated. The thoracic magnetic resonance imaging revealed vertebral fracture and an epidural mass that demonstrated low intensity on both T2- and T1-weighted images at the T9/10 dorsal side of the central canal. This lesion is larger in size than that observed in the previous 2 months. Her laboratory data showed signs of infection, and only decompression surgery without fixation for treatment and diagnosis was performed. Histopathological examination was consistent with tumoral calcinosis. Postoperatively, the patient's white cell count and CRP concentration were normalized. We found that tumoral calcinosis can occur at the thoracic level on the basis of the spinal instability due to the vertebral compression fracture and the accompanying increase in inflammation indicated by increased white blood cell count and CRP concentration., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 Isamu Miura et al.)

Spinal subdural abscesses are rare lesions. We report the case of surgical site infection complicated with meningitis and rapidly progressive spinal subdural abscess caused by P. aeruginosa following transforaminal lumbar interbody fusion (TLIF). A 72-year-old woman was admitted to our hospital complaining of drop foot syndrome and sciatica caused by stenosis of the L5/6 intervertebral foramen accompanied by L5 lumbar vertebral fracture. Accordingly, TLIF of L5-L6 and balloon kyphoplasty of L5 were performed. On the 3rd postoperative day (POD), she was diagnosed with surgical site infection complicated with bacterial meningitis. Subcutaneous fluid, blood, and cerebrospinal fluid cultures indicated P. aeruginosa . On the 7 th POD, a repeat MRI showed a large dorsal fluid collection consistent with a subdural infection and massive cauda equina compression. We performed debridement and instrument removal and found a dural laceration that was not observed during the first operation. An intraoperative insensible dural laceration may cause bacteria intrusion into the subdural space., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 Isamu Miura et al.)

Background: Meningeal melanocytoma is a rare benign lesion found in the central nervous system. Preoperative diagnosis of meningeal melanocytoma is often a diagnostic challenge, as the clinical and neurologic features are often nonspecific. Various characteristics, including the natural course of this tumor, remain poorly understood. We report a case of a rapidly growing dumbbell-shaped melanocytoma compressing the spinal cord that manifested 2 years after a tumor was identified at the right C2-C3 foramen., Case Description: A 40-year-old, right-handed man presented with a 2-month history of right palm and left leg numbness. Magnetic resonance imaging of the cervical spine showed a dumbbell-shaped tumor at the right C2-C3 foramen with extension into the central canal. The lesion was hyperintense on T1-weighted images and hypointense to isointense on T2-weighted images. Contrast enhancement was not visualized clearly. Fluorodeoxyglucose-positron emission tomography with computed tomography showed intense uptake in the lesion. The patient's history included a small lesion that had been localized at the right C2-C3 foramen 2 years before admission. The pathologic findings were consistent with melanocytoma., Conclusions: It is important to include meningeal melanocytoma in the differential diagnosis of dumbbell tumors, as meningeal melanocytomas may show rapid progression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ganglioneuroma is a well-differentiated benign tumor that develops from the ganglion cells of the posterior mediastinum, retroperitoneum, cervical spine, and adrenal glands. The paravertebral body, in which the sympathetic trunk exists, is a common tumor site, and tumor sometimes invades the spinal canal through the intervertebral foramen. There have been no reports regarding tumors with intradural and extradural continuity. We report a paravertebral ganglioneuroma extending between the intradural and extradural spaces and its surgical treatment., Case Description: A 33-year-old man was admitted to the hospital with progressive left lower limb numbness. A dumbbell-type tumor progressing to the spinal canal via the left intervertebral foramen from the paravertebral body at L1-2 was detected, and intradural calcified lesions were found. Pathologic examination of a computed tomography-guided biopsy sample revealed a ganglioglioma. The extradural tumor was removed; however, the left lower limb pain gradually worsened. As complete block was observed on myelography, the intradural tumor was removed 8 months later. Intraoperative findings revealed that the intradural and extradural tumors were continuous through the L1 nerve root., Conclusions: This is the first known reported case of paravertebral ganglioneuroma presenting in continuity between the intradural and extradural spaces., (Copyright © 2019 Elsevier Inc. All rights reserved.)

It is difficult to treat atlantoaxial instability in patients with a high-riding vertebral artery or anomalies of the craniocervical junction. We report 2 successful cases in which the transspinal canal screwing technique was used because of difficulties performing conventional fixation methods. Case 1: A 78-year-old woman suffered from progressive myelopathy due to severe spinal cord compression with a congenital anomaly of the craniovertebral junction. Bilateral transspinal canal screws from the axis body with spondylolisthesis to the dens were inserted by retracting the dural sac medially after foramen magnum decompression and cervical laminoplasty. Case 2: A 20-year-old man with a spinal deformity due to Loeys-Dietz syndrome presented to our hospital for treatment of syringomyelia. He had no obvious neurological deficits, but spinal cord compression due to right atlantoaxial rotating dislocation was observed. A screw was inserted from the vertebral body of the axis to the right lateral mass of the atlas via the spinal canal after laminectomy of the atlas. The transspinal canal screwing technique is useful for treating atlantoaxial instability in cases where other fixation methods are difficult.

Introduction: Japan has many patients with osteoporosis; however, only about one-fifth of these patients receive treatment. Although some treatment guidelines exist for osteoporosis, the number of newly diagnosed patients with osteoporotic compression fractures is increasing and protocols for treatment of osteoporotic compression fractures vary from one hospital to another. This study aims to investigate the availability of early balloon kyphoplasty(BKP)in relation to our treatment strategy for osteoporotic compression fractures., Methods: In our hospital, patients diagnosed with osteoporotic compression fractures were treated conservatively with a corset and rehabilitation. In cases where pain was prolonged and computed tomography(CT)imaging revealed formation of a cavity, we performed BKP. We divided the patients admitted between April 2016 and December 2016 with osteoporotic compression fractures into 2 groups, based on whether they received conservative treatment or BKP. We assessed the patients' age, fracture site, CT and MRI findings, bone density, Numerical Rating Scale(NRS), duration of hospital stay, and outcomes., Results: In the BKP group, the number of Th12 and L1 compression fractures was higher than fractures to other vertebral bodies. No difference was observed in bone density, improvement of NRS, and outcomes between groups. CT cavity signs were more frequently observed in the BKP group than in the conservative group., Conclusions: This study establishes a correlation between the appearance of CT cavity sign and prolonged pain, which increases the likelihood of a patient undergoing BKP. The CT cavity sign and prolonged pain could be indicators of pre-stage pseudoarthrosis. BKP performed in the early stages of a fracture is safe and does not result in complications. However, BKP should be performed according to appropriate indications, including delayed neurological deficit, pain, and reduced bone adhesion.

Background Context: Neuroendocrine tumors (NETs) from tailgut cysts are rare; only 15 cases have been reported until now. A tailgut cyst with spinal cord tethering has not been previously reported, although both diseases are congenital anomalies in the early stage of gestation., Purpose: To report a rare case of NET from tailgut cyst associated with spinal cord tethering and review the literature., Study Design: Case report and literature review., Methods: We describe the clinical course of a 53-year-old man, who presented with gluteal pain and bladder dysfunction. Magnetic resonance images showed that a tumor of the sacral spinal canal extended into the retrorectal space and connected to a thickened fatty filum terminale, which was tethering the spinal cord., Results: Because of tumor malignancy on a computed tomography-guided biopsy and the imaging data of involvement of presacral lymph nodes, we performed total removal of the tumor. Pathologic examination revealed NET (Grade 2) arising from a tailgut cyst. The patient received somatostatin analog therapy after surgery, followed by local radiation because of the further enlargement of the lymph nodes. Later, we started everolimus therapy for the metastases to the retroperitoneal lymph nodes. He presented with no local recurrence or further disease progression at 28 months after surgery. The review indicated that tumors in Grade 2 or 3 showed progressive clinical course after surgery and three of seven patients with biopsy were misdiagnosed., Conclusions: The correct preoperative diagnosis of NETs from tailgut cysts is difficult, but extremely important because Grade 2 or 3 tumors show disease progression even after surgery. Presacral congenital tumors, such as tailgut cysts, have the potential of malignant transformation into neuroendcrine tumors or adenocarcinomas. Comorbidity of spinal cord tethering and tailgut cyst suggests some relationship to common developmental errors in embryogenesis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Effects of keishibukuryogan (KBG) on platelet aggregation were investigated. To ensure the specificity of KBG, tokishakuyakusan (TSS) and kamisyoyosan (KSS), which are known to have platelet aggregation-inhibiting effects, and rikkunshito (RKT) and shakuyakukanzoto (SKT), which are considered to be devoid of such effects, were used for comparison. The platelet aggregation of each test drug was measured by the screen filtration pressure method using whole blood of guinea pigs and expressed as a collagen-induced pressure rate (%) or a collagen concentration required for 50% increase in the pressure rate (PATI value). KBG suppressed the collagen-induced whole blood pressure rate increase and increased the PATI value, like TSS and KSS. Neither RKT nor SKT showed these effects. The Moutan cortex and Cinnamomi cortex, the constituent crude drugs of KBG, showed KBG-like pressure rate suppression and PATI-increasing effects. Furthermore, paeonol, a representative component of Moutan cortex, and aspirin which is known to have platelet aggregation-inhibiting activity (COX-1 inhibitor) also showed similar effects. These results suggest that the platelet aggregation-inhibiting activity of the constituent crude drugs Moutan cortex and Cinnamomi cortex is involved in the improving effects of KBG on impaired microcirculation and that paeonol plays a role in these effects.

Objective: The aim of the present study was to clarify the changes in circulating cytokines and chemokines in women during the menopausal transition by using a detailed classification., Materials and Methods: A total of 554 women were recruited for this study from the outpatient clinic of the Department of Obstetrics and Gynecology, Tokushima University Hospital. We divided the women into seven stages by menstrual regularity and FSH level: mid-reproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause, early postmenopause and late postmenopause. We measured serum concentrations of nine cytokines (IL-1β, IL-5, IL-6, IL-7, IL-8, IL-10, TNF-α, MIP-1β and MCP-1)., Results: Serum IL-8 concentrations in postmenopausal women were significantly (p = 0.001) higher than those in women in the mid- or late reproductive stage and women in early or late menopausal transition. Serum MCP-1 levels in women in late menopausal transition and postmenopause were significantly (p < 0.001) higher than those in women in the mid- or late reproductive stage and women in early menopausal transition. MCP-1 level showed a significant positive correlation (r = 0.215, p < 0.01) with FSH level in women in menopausal transition., Conclusion: By using a detailed classification of menopausal transition, patterns of changes in IL-8 and MCP-1 levels during the menopausal transition were found to be different. IL-8 level showed a high level after menopause, while MCP-1 level showed a high level in menopausal transition. MCP-1 may be sensitive to hormonal change and may be involved in the development of estrogen deficiency diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Shakuyakukanzoto (SKT) composed of Glycyrrhizae radix (G. radix) and Paeoniae radix (P. radix) has been traditionally used in Japan, Korea and China as an antispasmodic drug for the treatment of skeletal muscle cramps and intestinal cramps., Aim of This Study: To evaluate the antispasmodic activity of SKT and its two components, as well as to identify the key constituents of the components which mediate this effect in skeletal muscles in vivo., Materials and Methods: An experimental cramp model was constructed to evaluate the effects of peripherally-acting muscle relaxants on electrically-induced cramps under physiological conditions. This was accomplished by surgically isolating the motor supply to the gastrocnemius muscle in an anesthetized rat and delivering electrical stimuli to an isolated tibial nerve to induce tetanic contractions. We first tested dantrolene, a well-known peripherally-acting relaxant, to determine the sensitivity and reliability of our experimental model. We then evaluated the effects of SKT, P. radix, G. radix, and the eight active constituents of G. radix against tetanic contractions., Results: We found that dantrolene (10 and 30 mg/kg, i.d.) rapidly and significantly inhibited tetanic contractions (P<0.01) irrespective of dose. SKT (0.5, 1.0, and 2.0 g/kg, i.d.) and G. radix (0.5 and 1.0 g/kg, i.d.) also significantly inhibited tetanic contractions (P<0.01) but in a dose-dependent manner owing to the actions of six of the eight active constituents in G. radix (liquiritin apioside, liquiritigenin, isoliquiritin apioside, isoliquiritigenin, glycycoumarin, and glycyrrhetinic acid, 20 μmol/kg, i.v.). These constituents, which include flavonoids, a triterpenoid, and a courmarin derivative, demonstrated temporal variations in their inhibitory activity. In contrast, P. radix (0.5 and 1.0 g/kg, i.d.) did not show a statistically significant antispasmodic effect in our study; however, we previously found that it had a significant antinociceptive effect., Conclusions: Our findings show that SKT inhibits tetanic contractions in vivo and that G. radix is the main antispasmodic component due to the actions of its active constituents, thus supporting the traditional use of SKT. We further propose that SKT containing the antispasmodic G. radix and antinociceptive P. radix is a pharmaceutically elegant option for muscle cramps as treatment requires a two-pronged approach, i.e., inhibition of hyperexcitable skeletal tissues and modulation of the pain accompanying cramps., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

There have been few clinical studies in the area of cervical spine that focused on surgery for treating degenerative lumbar disease in patients with rheumatoid arthritis (RA). High rates of wound complications and instrumentation failure have been reported more for RA than for non-RA patients, although clinical outcomes are similar between the two groups. Lumbar canal stenosis in RA is caused not only by degeneration but also by RA-related spondylitis, which includes facet arthritis and inflammation around the vertebral endplate. The pitfalls in surgical management of lumbar canal stenosis in RA patients are highlighted in this study. The study reviewed 12 patients with RA, who were surgically treated for lumbar canal stenosis. Two out of five patients with pulmonary fibrosis died of worsened pulmonary condition, even though there were no perioperative pulmonary complications. Two patients with pedicle screw fixation showed no instrumentation failure, but two patients with spinous process fixation needed re-operation or vertebral fracture. Surgical treatment for lumbar canal stenosis in RA patients needs to be individually adjusted. Preoperative assessments and treatments of pulmonary fibrosis and osteopenia are essential. Surgery for lumbar canal stenosis with RA should be deferred for patients with advanced pulmonary fibrosis because of its potential life-threatening risk. Fusion surgery is indicated only in patients with kyphosis or severe symptoms caused by intervertebral instability. Pedicle screw fixation with hydroxyapatite granules or sublaminar tape is recommended. Closer follow-up after surgery is necessary because of possible delayed wound infection, instrumentation failure, pathological fracture, and respiratory deterioration.

Objective: The purpose of this study was to determine (1) the influence of estrogen deficiency induced by gonadotropin-releasing hormone (GnRH) agonist administration on insulin sensitivity as well as hormones and factors related to insulin resistance and (2) the differences in the influence for these parameters by the degree of basal insulin sensitivity., Methods: Thirty-five women diagnosed with leiomyoma were enrolled in this study. Serum levels of fasting glucose, insulin, sex steroid hormones, sex hormone-binding globulin (SHBG), vascular inflammatory markers and cytokines before and at 6months after commencement of GnRH agonist administration were examined., Results: In all women, levels of insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR) were not significantly changed. However, in women who had a low HOMA-IR before treatment, levels of insulin, glucose and HOMA-IR showed significant increases and total testosterone level showed a significant decrease. In women who had a high HOMA-IR, levels of insulin, HOMA-IR and SHBG were significantly decreased and levels of highly sensitive C-reactive protein, soluble intercellular adhesion molecule-1, E-selectin and monocyte chemoattractant protein-1 were significantly increased., Conclusion: Change in insulin sensitivity caused by GnRH agonist administration for premenopausal women with leiomyoma differs depending on baseline insulin sensitivity before treatment., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Proteus syndrome is a rare, sporadic, hamartomatous disorder manifesting with multifocal overgrowth of tissue. The features seem to develop most often during childhood. Vertebral overgrowth with severe spinal canal stenosis is unusual, although scoliosis with abnormal vertebral bodies is one of the typical features of Proteus syndrome. We report a case of Proteus syndrome with severe spinal canal stenosis, scoliosis, cervical kyphosis, and thoracic deformity with airway obstruction because of asymmetrical overgrowth of vertebrae and ribs associated with a tethered cord, lipomas, strawberry hemangioma, flat nasal bridge, and bilateral hypoplasty of the first metatarsal bones with hyperplasty of soft tissue.

Yokukansan, one of the traditional Japanese herbal medicines, ameliorated neuropathic pain symptoms in patients. In this study, we investigated the effects of yokukansan on neuropathic pain in chronic constriction injury (CCI) model. Oral administration of yokukansan significantly inhibited mechanical and cold allodynia in the von Frey hair or acetone test, respectively. In comparison, amitriptyline, a tricyclic antidepressant, demonstrated moderate, but not significant, antiallodynic effects in the mechanical and cold tests. Yokukansan significantly inhibited the cerebrospinal fluid dialysate level of glutamate that had increased by the stimulation of brush or acetone. Glutamate transporter inhibitors, DL-threo-beta-hydroxy aspartate and dihydrokainate, decreased the yokukansan-induced antiallodynic actions in CCI rats. Our results suggest that yokukansan was confirmed to have antiallodynic effects in CCI rats, which are related to a blockade of glutamatergic neurotransmission via activation of glutamate transporters in the spinal cord.

Background: Shakuyakukanzoto (SKT) has been shown to modulate nociception in streptozotocin-induced diabetic mice via selective activation of the descending noradrenergic systems. However, the active components of SKT that exert the analgesic effect remain unknown. Here, we administered Glycyrrhizae radix (G. radix), Paeoniae radix (P. radix), and the two active constituents of P. radix, paeoniflorin and albiflorin, to determine the components that stimulate spinal α₂-adrenoceptors by promoting noradrenaline release., Methods: The two SKT components were separately administered to diabetic and non-diabetic mice. A tail-pressure test was used to determine the nociceptive threshold between 0 and 3h after oral dosing. The time-course profiles of the nociceptive threshold (g) and the area under the time response curve (AUC) were evaluated. Yohimbine, an α₂-adrenoceptor antagonist, was intrathecally injected 15 min after paeoniflorin administration., Results: P. radix and G. radix did not induce significant antinociception in non-diabetic mice. However, P. radix (250, 500 mg/kg) dose-dependently and significantly increased the nociceptive threshold in diabetic mice between 0.5 and 2 h after administration, whereas all the tested doses of G. radix did not increase the nociceptive threshold. Both paeoniflorin (30 mg/kg) and albiflorin (10 mg/kg) significantly elevated the nociceptive threshold between 0.5 and 3h and between 0.5 and 1h after administration, respectively. The antinociceptive effect of paeoniflorin (30 mg/kg) was completely abolished by yohimbine., Conclusion: Our findings suggest that paeoniflorin is the key antinociceptive component in SKT that increases noradrenaline release and activates α₂-adrenoceptors to modulate spinal nociceptive transmission in diabetic neuropathy., (Copyright © 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

The aim of the present study was to determine the influence of acute estrogen deficiency induced by administration of a gonadotropin-releasing hormone (GnRH) agonist on circulating levels of cytokines and chemokines. Eighty-three women with uterine leiomyoma were assigned in open, parallel-group fashion to a no-treatment (control) group and a GnRH-agonist group. Serum levels of nine cytokines and chemokines as well as vascular inflammatory markers were measured. Serum levels of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor-α (TNFα) in the GnRH-agonist group were increased significantly at 6 months. There were also significant differences in percentage changes in interleukin (IL)-6, IL8, MCP1, and macrophage inflammatory protein-1β (MIP1β) between the control and GnRH agonist groups. Soluble intercellular adhesion molecule-1 (sICAM1) and E-selectin levels showed significant increases in the GnRH agonist group at 6 months. Serum MCP1 concentrations showed weak correlations with levels of sICAM and E-selectin. We conclude that a hypo-estrogenic state due to administration of a GnRH agonist increases circulating levels of cytokines and chemokines, especially MCP1., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: The effects of the Japanese traditional medicines keishibukuryogan and kamishoyosan on circulating cytokines were examined to clarify the difference in the actions of Japanese traditional medicines in women with hot flashes., Methods: Seven premenopausal, 51 perimenopausal, 45 spontaneously postmenopausal and 17 surgically postmenopausal women who had complained of hot flashes were enrolled in this study. Eighty women who hoped to receive Japanese traditional medicines were randomly assigned in open, parallel-group fashion to a keishibukuryogan group or kamishoyosan group. Forty women who did not want any treatment for hot flashes were followed up for 6 months as a control group. Serum levels of cytokines were measured using a multiplexed human cytokine assay., Results: The proportions of responders in women treated with keishibukuryogan and kamishoyosan were 73.7% and 69.2%, respectively. Serum monocyte chemotactic protein-1 level in women treated with keishibukuryogan decreased significantly (P = 0.0037). On the other hand, concentrations of interleukin (IL)-6 and macrophage inflammatory protein-1β in women treated with kamishoyosan decreased significantly (P = 0.019 and P = 0.039, respectively). In both keishibukuryogan and kamishoyosan responder groups, serum IL-8 concentrations were reduced significantly (P = 0.021 and P = 0.014, respectively)., Conclusions: Both treatments with keishibukuryogan and kamishoyosan reduce the circulating IL-8 level, which is involved in thermoregulation in perimenopausal women with hot flashes. In addition, keishibukuryogan decreases circulating monocyte chemotactic protein-1 level in postmenopausal women.

Circulating ghrelin concentration regulates appetite behavior, but no study thus far has focused on the role of central ghrelin in anorexia after chemotherapy. To clarify the action mechanisms of rikkunshito (RKT), a traditional Japanese medicine, on cisplatin-induced anorexia, we attempted to elucidate its effect on hypothalamic ghrelin receptor expression in cisplatin-induced anorexia. We first examined the effects of an intracerebroventricular (ICV) injection of exogenous ghrelin on food intake with or without cisplatin treatment, and the effects of cisplatin or m-chlorophenylpiperazine (mCPP), a 5-HT2C receptor agonist, on hypothalamic growth hormone secretagogue receptor 1a (GHS-R1a) mRNA expression. To identify the mechanism of cisplatin-induced decrease in hypothalamic GHS-R1a mRNA expression, we evaluated the effects of SB242084HCl, a 5-HT2C receptor antagonist, and RKT on hypothalamic GHS-R1a gene expression, along with the effect of coadministration of a GHS-R1a antagonist on decreased food intake. Compared to vehicle controls, an ICV-injected rat ghrelin failed to inhibit the decrease in food intake in cisplatin-treated rats. Hypothalamic GHS-R1a gene expression was significantly reduced after cisplatin or mCPP treatment, and the induced decrease was reversed by SB242084HCl or RKT, but not granisetron or ondansetron, both of which are 5-HT3 receptor antagonists. Their suppressive effect on the decrease in food intake was abolished by coadministration of the GHS-R1a antagonist. Administration of RKT or SB242084HCl reversed the decrease in food intake induced by mCPP injection. The improvement by RKT on decreased food intake after cisplatin treatment was partly mediated by hesperidin and isoliquiritigenin, components of RKT. Cisplatin-induced anorexia may worsen because of decreased hypothalamic GHS-R1a gene expression. A 5-HT2C receptor antagonist and RKT suppressed cisplatin-induced anorexia by inhibiting reduction of GHS-R1a signal transduction in the hypothalamus., (Copyright 2010 Elsevier B.V. All rights reserved.)

Aim of Study: Luteinizing hormone-releasing hormone (LH-RH) has been suggested as an inducer of centrally mediated elevation of skin temperature, and calcitonin gene-related peptide (CGRP) is one of the potent vasodilator neuropeptides that has been suggested as an inducer of peripherally mediated elevation of skin temperature. We investigate the effect of the Japanese herbal medicine Tokaku-jyoki-to using two rat-models for menopausal hot flash., Materials and Methods: Tokaku-jyoki-to used in present study was prepared as a spray-dried powder from hot-water extract. Skin temperature was measured by thermister thermometer. Estrogen receptor (ER) binding assay of Tokaku-jyoki-to extract was performed using human recombinant ERalpha or ERbeta., Results: Oral Tokaku-jyoki-to (1000 mg/kg) restored skin temperature rise induced by LH-RH or CGRP in ovariectomized (OVX) rats as well as subcutaneous 17beta-estradiol (0.010 mg/kg) did. Tokaku-jyoki-to did not affect the lower concentration of plasma estradiol and the decreased uterine weight due to ovariectomy, although the hormone replacement of 17beta-estradiol restored them. In estrogen receptor ligand-binding study, Tokaku-jyoki-to extract bound to human ERalpha poorly and did not bound to human ERbeta., Conclusions: These results suggest that Tokaku-jyoki-to, which appears to contain organ-specific selective estrogen receptor modulator, may be useful for the treatment of hot flashes in patients for whom estrogen replacement therapy is contraindicated as well as menopausal women.

Effects of yokukansan (TJ-54) on memory disturbance and behavioral and psychological symptoms of dementia (BPSD) were investigated in thiamine-deficient (TD) rats which were produced by feeding a TD diet for 37 d. Daily oral administration of TJ-54 (0.5, 1.0 g/kg) ameliorated the memory disturbance, anxiety-like behavior, the increase in aggressive behaviors, the decrease in social behaviors, and several neurological symptoms including opisthotonus observed in TD rats, in a dose-dependent manner. In addition, histopathological examinations showed that TJ-54 inhibited the degeneration of neuronal and astroglial cells in the brain stem, hippocampus and cortex in TD rats. Microdialysis experiments showed that TJ-54 inhibited extracellular glutamate rise in the ventral posterior medial thalamus in TD rats. These results suggest that TJ-54 possesses the preventive or progress inhibitive effect against the development of memory disturbance and BPSD-like behaviors induced by the degeneration of neuronal and astroglial cells resulting from TD. TJ-54 may inhibit glutamate-mediated excitotoxicity as one of mechanisms.