1.Yokukansan Suppresses Gastric Hypersensitivity and Eosinophil-associated Microinflammation in Rats With Functional Dyspepsia
Shaoqi DUAN ; Nobuko IMAMURA ; Takashi KONDO ; Hirosato KANDA ; Yoko KOGURE ; Takuya OKUGAWA ; Masashi FUKUSHIMA ; Toshihiko TOMITA ; Tadayuki OSHIMA ; Hirokazu FUKUI ; Koichi NOGUCHI ; Yi DAI ; Hiroto MIWA
Journal of Neurogastroenterology and Motility 2022;28(2):255-264
Background/Aims:
Herbal medicine is an important complementary therapy for functional dyspepsia (FD). However, its effect against gastric hypersensitivity in patients with FD has rarely been evaluated. Yokukansan (YKS), a traditional Japanese herbal medicine, is effective against neuropathic and inflammatory pain. This study aims to use a maternal separation (MS) stress-induced FD model to investigate the effects of YKS against gastric hypersensitivity, gastric motility, and duodenal micro-inflammation.
Methods:
The MS stress model was established by separating newborn Sprague-Dawley rats from their mothers for 2 hours a day from postnatal days 1 to 10. At the age of 7-8 weeks, the rats were treated with YKS at a dose of 5 mL/kg (1 g/kg) for 7 consecutive days. AfterYKS treatment, electromyographic activity in the acromiotrapezius muscle by gastric distention and the gastric-emptying rate were assessed. Immunohistochemical analysis of eosinophils in the duodenum and phosphorylated extracellular signal-regulated kinase(p-ERK) 1/2 in the spinal cord was performed.
Results:
YKS treatment suppressed MS stress-induced gastric hypersensitivity and decreased the elevated levels of p-ERK1/2 in the spinal cord.In the gastroduodenal tract, YKS inhibited eosinophil-associated micro-inflammation but did not improve gastric dysmotility.
Conclusions
YKS treatment improved gastric hypersensitivity by alleviating eosinophil-associated micro-inflammation in the gastroduodenal tract.This treatment may be considered an effective therapeutic option for epigastric pain and micro-inflammation in patients with FD.
2.Total Cholesterol Level for Assessing Pancreatic Insufficiency Due to Chronic Pancreatitis.
Kenji HIRANO ; Tomotaka SAITO ; Suguru MIZUNO ; Minoru TADA ; Naoki SASAHIRA ; Hiroyuki ISAYAMA ; Miho MATSUKAWA ; Gyotane UMEFUNE ; Dai AKIYAMA ; Kei SAITO ; Shuhei KAWAHATA ; Naminatsu TAKAHARA ; Rie UCHINO ; Tsuyoshi HAMADA ; Koji MIYABAYASHI ; Dai MOHRI ; Takashi SASAKI ; Hirofumi KOGURE ; Natsuyo YAMAMOTO ; Yosuke NAKAI ; Kazuhiko KOIKE
Gut and Liver 2014;8(5):563-568
BACKGROUND/AIMS: To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice. METHODS: A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups. RESULTS: The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052). CONCLUSIONS: Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.
Adult
;
Aged
;
Aged, 80 and over
;
Cholesterol/*blood
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Cholinesterases/blood
;
Diabetes Mellitus, Type 2/complications
;
Exocrine Pancreatic Insufficiency/*blood/etiology
;
Female
;
Follow-Up Studies
;
Humans
;
Liver Cirrhosis, Alcoholic/blood
;
Male
;
Middle Aged
;
Nutritional Status
;
Pancreas/enzymology
;
Pancreatitis, Alcoholic/blood/complications
;
Pancreatitis, Chronic/blood/*complications
;
Serum Albumin/analysis
3.A Novel, Fully Covered Laser-Cut Nitinol Stent with Antimigration Properties for Nonresectable Distal Malignant Biliary Obstruction: A Multicenter Feasibility Study.
Hiroyuki ISAYAMA ; Kazumichi KAWAKUBO ; Yousuke NAKAI ; Kouta INOUE ; Chimyon GON ; Saburo MATSUBARA ; Hirofumi KOGURE ; Yukiko ITO ; Takeshi TSUJINO ; Suguru MIZUNO ; Tsuyoshi HAMADA ; Rie UCHINO ; Koji MIYABAYASHI ; Keisuke YAMAMOTO ; Takashi SASAKI ; Natsuyo YAMAMOTO ; Kenji HIRANO ; Naoki SASAHIRA ; Minoru TADA ; Kazuhiko KOIKE
Gut and Liver 2013;7(6):725-730
BACKGROUND/AIMS: Stent migration occurs frequently, but the prevention of complications resulting from covered self-expandable metal stents (C-SEMSs) remains unresolved. We prospectively assessed a newly developed C-SEMS, a modified covered Zeo stent (m-CZS), in terms of its antimigration effect. METHODS: Between February 2010 and January 2011, an m-CZS was inserted into 42 patients (31 initial drainage cases and 11 reintervention cases) at a tertiary referral center and three affiliated hospitals. The laser-cut stent was flared for 1.5 cm at both ends, with a 1 cm raised bank located 1 cm in from each flared end. The main outcome of this study was the rate of stent migration, and secondary outcomes were the rate of recurrent biliary obstruction (RBO), the time to RBO, the frequencies of complications, and overall survival. RESULTS: Of the 31 patients with initial drainage, stent migration occurred in four (12.9%, 95% confidence interval, 5.1% to 29.0%), with a mean time of 131 days. RBO occurred in 18 (58%), with a median time to RBO of 107 days. Following previous C-SEMS migration, seven of 10 patients (70%) did not experience m-CZS migration until death. CONCLUSIONS: m-CZSs with antimigration properties effectively, although not completely, prevented stent migration after stent insertion.
Aged
;
Aged, 80 and over
;
Alloys
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Carcinoma/*complications
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Cholestasis/etiology/*therapy
;
Digestive System Neoplasms/*complications
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Drainage
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Equipment Design
;
Feasibility Studies
;
Female
;
Humans
;
Kaplan-Meier Estimate
;
Lymphatic Metastasis
;
Male
;
Middle Aged
;
*Prosthesis Failure
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Recurrence
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Reoperation
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*Stents/adverse effects
;
Time Factors
4.Simultaneous Duodenal Metal Stent Placement and EUS-Guided Choledochoduodenostomy for Unresectable Pancreatic Cancer.
Kazumichi KAWAKUBO ; Hiroyuki ISAYAMA ; Yousuke NAKAI ; Naoki SASAHIRA ; Hirofumi KOGURE ; Takashi SASAKI ; Kenji HIRANO ; Minoru TADA ; Kazuhiko KOIKE
Gut and Liver 2012;6(3):399-402
Patients with pancreatic cancer frequently suffer from both biliary and duodenal obstruction. For such patients, both biliary and duodenal self-expandable metal stent placement is necessary to palliate their symptoms, but it was difficult to cross two metal stents. Recently, endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CDS) was reported to be effective for patients with an inaccessible papilla. We report two cases of pancreatic cancer with both biliary and duodenal obstructions treated successfully with simultaneous duodenal metal stent placement and EUS-CDS. The first case was a 74-year-old man with pancreatic cancer. Duodenoscopy revealed that papilla had been invaded with tumor and duodenography showed severe stenosis in the horizontal portion. After a duodenal uncovered metal stent was placed across the duodenal stricture, EUS-CDS was performed. The second case was a 63-year-old man who previously had a covered metal stent placed for malignant biliary obstruction. After removing the previously placed metal stent, EUS-CDS was performed. Then, a duodenal covered metal stent was placed across the duodenal stenosis. Both patients could tolerate a regular diet and did not suffer from stent occlusion. EUS-CDS combined with duodenal metal stent placement may be an ideal treatment strategy in patients with pancreatic cancer with both duodenal and biliary malignant obstruction.
Aged
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Choledochostomy
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Constriction, Pathologic
;
Diet
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Duodenal Obstruction
;
Duodenoscopy
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Humans
;
Middle Aged
;
Pancreatic Neoplasms
;
Stents
5.Are Kampo Formulations able to be Selected According with the Name of Diseases? Or, are They able to be Selected Exclusively According with \lq\lqSho\rq\rq (Kampo Diagnosis)?
Toshiaki KOGURE ; Takashi KANO ; Takahisa USHIROYAMA ; Toshiaki KITA ; Mikikazu YAMAGIWA
Kampo Medicine 2007;58(1):15-47
Medicine, Kampo
;
Names
;
Disease
;
Diagnosis
6.A Study on a Quantity of Imbibition of Natural Medicines at Boiling.
Shin MATSUURA ; Naotoshi SHIBAHARA ; Takashi ITOH ; Hirotoshi FUSHIMI ; Toshiaki KOGURE ; Hirozo GOTO ; Yutaka SHIMADA ; Katsutoshi TERASAWA
Kampo Medicine 2003;54(1):199-208
As many natural medicines absorb water at boiling, yields of the decoctions are affected by absorbed water. Therefore, we examined the quantity of imbibition of each crude drug at boiling. We used 75 kinds of crude drugs. After boiling 600ml of water, each natural medicine was boiled for 70 minutes. The medicine was left for 60 minutes, and then boiled again for 20 minutes. The quantity of imbibition of each natural medicine was measured at 10, 20, 30, 40, 60, 130, and 150 minutes. The maximum data among the quantity of imbibition at each point was labeled “maximum quantity of imbibition.” With regard to the maximum quantity of imbibition in natural medicines of plant origin, the range was from a maximum of 69.10g in Chrisanthemi Flos to a minimum of 3.26g in Persicae Semen. The average maximum quantity of imbibition was 22.51±13.00g, and there were large differences among each of the natural medicines. The quantity of imbibition at 10 minutes or 20 minutes was above 80% of each maximum quantity of imbibition on many crude drugs, but that gradually increased over the time course for some crude drugs.
7.Preliminary Study on Unreliability of Lymphocyte Stimulating Test for Kampo Medicine
Naoki MANTANI ; Harumi MATSUDA ; Eiichi TAHARA ; Shinya SAKAI ; Toshiaki KOGURE ; Hirozo GOTO ; Naotoshi SHIBAHARA ; Toshiaki KITA ; Takahiro SHINTANI ; Yutaka SHIMADA ; Takashi ITO ; Katsutoshi TERASAWA
Kampo Medicine 2001;51(5):1093-1099
We performed a preliminary study of the reliability of the lymphocyte stimulating test (LST) for Kampo medicine. LST for three kinds of Kampo medicines was performed in both a Kampo-administrated group and a non-administrated group. LST for each of the medicines was negative for seven of eight subjects in the non-administrated group, but was negative for four of 11 subjects in the Kampo-administrated group. The LST-positive participants had no allergic state, and some among them were negative in challenge test. This preliminary study suggests that LST for Kampo medicine is likely to be false-positive.
8.Effects of Kampo Treatment on the Development and Progression of Diabetic Microangiopathy.
Hiroaki HIKIAMI ; Naotoshi SHIBAHARA ; Hirozo GOTO ; Toshiaki KOGURE ; Kazuhiko NAGASAKA ; Toshiaki KITA ; Yutaka SHIMADA ; Takashi ITOH ; Katsutoshi TERASAWA
Kampo Medicine 2000;50(5):841-850
We investigated the effects of Kampo treatment on the development and progression of diabetic microangiopathy in 141 patients (95 male and 46 female patients, mean±S.D., 61.3±10.1 years) with non-insulin dependent diabetes mellitus. To this purpose, we examined the severity of diabetic microangiopathy with respect to the duration of suffering from diabetes mellitus as well as the duration of the condition after the commencement of Kampo treatment. We obtained the following results. 1) The significantly lighter the severity of diabetic nephropathy was, the longer its duration under Kampo treatment was. 2) In the group of shorter duration of suffering from diabetes mellitus, although there was no statistical significance, the longer the duration under Kampo treatment was, the lighter the severity of diabetic neuropathy and retinopathy was. But, there was no significant difference in the longer duration of suffering. It was suggested that the combination therapy with Kampo treatment was effective for diabetic microangiopathy.
9.Two Cases of Rheumatoid Arthritis Treated with Shikunshi-to-kami-ho.
Naoki MANTANI ; Toshiaki KOGURE ; Yutaka SHIMADA ; Takashi ITO ; Katsutoshi TERASAWA
Kampo Medicine 2000;50(5):861-867
We present here two cases of rheumatoid arthritis (RA) treated with Shikunshi-to-ka-keishi-shakuyaku-yokuinin. Case 1 was a 71-year-old female who had been suffering from RA for two years and had been treated with western medicines. Keishi-ni-eppi-itto-ka-ryojutsubu-to offered some degree of palliation at first, but soon came to cause itchy eruptions and anorexia. On the other hand, treatment with Shikunshi-to-kami-ho (described above) for nine months achieved complete remission without any adverse reactions. Case 2 was a 52-year-old female who was diagnosed as RA in 1989 and had discontinued treatments with a variety of DMARDs (disease modifying anti-rheumatic drugs) because of adverse reactions such as eruptions, anorexia, and loss of hair. Moreover, many Kampo medicines with low-dose steroids were less effective. Shikunshi-to-kami-ho, which was administered after Kampo-medicine-induced liver damage, produced clinical effects to some degree. Shikunshi-to-kami-ho may be useful in the treatment of RA patients who have developed adverse reactions such as eruptions, liver damage, and anorexia.
10.The Effects of Unkei-To on Patients with Primary Sjoegren's Syndrome.
Toshiaki KOGURE ; Michio WATANABE ; Takashi ITOH ; Yutaka SHIMADA ; Katsutoshi TERASAWA
Kampo Medicine 1997;48(3):349-355
Unkei-to was used successfully to treat three patients with primary Sjögren's syndrome (pSjS). The first case was a 67-year-old woman. In April 1993, she visited Tonami General Hospital with the symptom of dry eyes. Her condition was diagnosed as pSjS from being antinuclear antibody (ANA) positive, dry eye, and decrease of saliva secretion. She used eye drops, but her dry eye did not improve, she visited our department in June 1995. Administration of Unkei-to improved her symptoms after 6 months of treatment.
The second case was a 73-year-old woman. In 1987, she was treated in our hospital for lumbago based on spondylosis. In 1991, she began to suffer from pain and swelling of the right sterno-clavicular joint (RSCJ) and was admitted. She was anti-SS-A/Ro ANA positive, schirmer's test was positive, lymphocyte infiltration was observed by lip biopsy, and thus pSjS was diagnosed. Treatment with Unkei-to resulted in the improvement of pain and swelling of RSCJ, as well as a decrease in serum C-reactive protein. But a favorable effect on dry mouth was not attained in this case.
The third case involved a 39-year-old woman who began to experience polyarthralgia and dry mouth in June 1991. She visited a neighborhood hospital and was diagnosed as pSjS from hyper γ-globulinemia, anti SS-A ANA positivity, and decrease of saliva secretion. She first visited our hospital in March 1994. We administered Keishikaryojutubu-to and improvement of polyarthralgia was observed. Subsequently, she suffered from symptoms of dry eye and dry mouth. We treated her with Unkei-to, which improved the symptoms of dryness, but not polyarthralgia in this case.
These observations suggest that Unkei-to might be a useful agent for the treatment of pSjS.


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