Kampo physicians in the Showa era, such as ARAKI Seiji and OTSUKA Keisetsu, had called raw ginger as the herbal medicament “ginger”, and processed or unprocessed dried ginger as the medicament “processed gin­ger”. However, many Kampo physicians in the present Japan call unprocessed dried ginger as the medicament “ginger”, and processed dried ginger as the medicament “processed ginger”. The aim of this study is to investi­gate the background of the process of this change from the Showa era to the present. We searched the defini­tions of the medicaments “ginger” and “processed ginger” in successive Japanese Pharmacopoeia editions and other related books describing these definitions. In Japanese Kampo medicine before the Showa era, the herbal medicament “ginger” had referred to raw ginger, and the medicament “processed ginger” had referred to proc­essed or unprocessed dried ginger. However, after the Heisei era, the medicaments “ginger” and “processed ginger” have referred to unprocessed dried ginger and processed dried ginger, respectively. And the raw ginger has been called as “preserved ginger”.

We investigated the decocting time to prepare the formulas containing unprocessed aconite root, such as shigyakuto, tsumyaku shigyakuto, and kankyobushito, which had been registered in “Shanghanlun” edited in Song Dynasty, using the weights and measures in Houhan Dynasty when the original “Shanghanlun” was regarded to have been established. Also the contents of aconitine-type diester alkaloids (ADA) eluted from unprocessed aconite root in the decoction were analyzed in time-dependent manners. As regards the modified formula for the “physically strong patients” in the texts of tsumyakushigyakuto in “Shanghanlun”, adding dried ginger was found to lead the decocting time to be shorter and the sum of ADA content in the decoction of the modified formula to increase about 20%. It was also found that the compositions of diterpene alkaloids derived from aconite root in kankyobushito decoction were highly different from those in shigyakuto decoction, containing less ADA and more aconine and hypaconine, due to the high pH of the decoction, which was the consequence of lacking glycyrrhiza in kankyobushito formula. It is suggested that the doctors in the era of “Shanghanlun” establishment may have carefully adjusted the contents of ADA in the decoctions using unprocessed aconite root by choosing co-decocted crude drugs.

Fecal microbiota transplantation (FMT) has been reported as a safe and effective therapy in patients with refractory and recurrent Clostridium difficile infection (CDI). FMT has also been reported as a promising therapy in patients with ulcerative colitis (UC). Both, CDI and UC, are believed to be caused by dysbiosis, such as altered compositions or decreased diversity of the intestinal microbiota. This report describes a patient with UC in remission with a second recurrent episode of CDI, who was treated with FMT. A single FMT performed via colonoscopy completely resolved the patient's diarrhea and eradicated C. difficile bacteriologically without any severe complications. Molecular biological analysis of the patient's fecal microbiota showed that FMT could dramatically change the altered composition of intestinal microbiota and restore its diversity. Despite the restoration of the intestinal microbiota, FMT could not prevent a relapse of UC in this patient. However, it improved the intestinal symptoms of CDI and could prevent further recurrences of CDI.
Clostridium difficile ; Clostridium ; Colitis, Ulcerative ; Colonoscopy ; Diarrhea ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Microbiota ; Recurrence ; Ulcer

The decoctions of unprocessed aconite root (uzu) were prepared with the tap water samples collected in Tianjin and Shanghai in China, and the contents of alkaloids in the decoctions were compared to those prepared with purified water or with tap water collected in Niigata, Japan. The contents of aconitine-type diester alkaloids (ADA) in the decoctions prepared with tap water collected in China were significantly lower than those with purified water or tap water in Niigata. It was speculated that this difference appeared by buffering effect of bicarbonic anion in tap water in China to decline pH of the decoction. When uzu was decocted with glycyrrhiza, ginger, or jujube, the contents of ADA in the decoctions exhibited the tendency to have higher levels than those prepared using unprocessed aconite root singly, and also this tendency was observed more remarkably when the decoctions were prepared with tap water collected in China. It was suggested that even the decocting period was fixed, unexpected change of the contents of ADAs might be induced by the differences in the properties of water used for decoction or the crude drugs decocted with aconite root. The physicians in the era when “Songban Shanghanlun” had established may have adjusted the contents of ADA in the decoction by carefully choosing the crude drugs combined to aconite root.

BACKGROUND/AIMS: Recent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn's disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD. METHODS: CD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mϕs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mϕs). Cytokine production by these in vitro differentiated macrophages in response to β-(1,3)-glucan was analyzed by flow cytometry. Expression of Dectin-1 was examined using flow cytometry, western blotting, and quantitative reverse transcription-polymerase chain reaction. Cytokine production by in vitro differentiated macrophages in response to β-(1,3)-glucan was measured in the presence of an anti-Dectin-1 receptor antagonist, anti-Syr, or an anti-Fas-1 antibody. Cytokine production by lamina propria mononuclear cells (LPMCs) derived from CD patients in response to β-(1,3)-glucan was also analyzed. RESULTS: Mγ-Mϕs produced a large amount of tumor necrosis factor-α (TNF-α) and interleukin-6 in response to β-(1,3)-glucan. Dectin-1 expression was significantly higher in Mγ-Mϕs than in M-Mϕs. The increase in TNF-α production by Mγ-Mϕs stimulated with glucan was reversed by blocking Dectin-1, Syr or Fas-1. LPMCs derived from CD patients stimulated with β-(1,3)-glucan produced significantly higher amount of TNF-α than LPMCs derived from UC patients. CONCLUSIONS: These results suggest that commensal fungal microbiota may contribute to the pathogenesis of CD by inducing macrophages-derived pro-inflammatory cytokines.
Blotting, Western ; Candida albicans* ; Candida* ; Crohn Disease* ; Cytokines* ; Flow Cytometry ; Fungi ; Healthy Volunteers ; Humans ; In Vitro Techniques ; Inflammation ; Interleukin-6 ; Macrophage Colony-Stimulating Factor ; Macrophages* ; Microbiota ; Monocytes ; Mucous Membrane* ; Necrosis ; Tumor Necrosis Factor-alpha

Ulcerative colitis (UC) is one of the major clinical phenotypes of inflammatory bowel diseases. Although 5-aminosalicylic acid (5-ASA) is widely used for UC and its efficacy and safety have been demonstrated, a few patients paradoxically develop a severe exacerbation of colitis by 5-ASA administration. It is crucial to know clinical features including endoscopic findings in this condition for making a correct diagnosis and a prompt decision to withdraw the medication. Here, we report case series with UC exacerbated by 5-ASA. Medical records of 8 UC patients experiencing an exacerbation of colitis after induction of 5-ASA that was improved by the withdrawal of 5-ASA but also re-aggravated by dose increase or re-administration of 5-ASA were reviewed. The patients were newly diagnosed with UC, started 5-ASA and developed an exacerbation in approximately 2 to 3 weeks. They did not appear to have systemic allergic reactions. Seven of the 8 patients had a high fever. Three of 5 patients who undertook total colonoscopy showed right-side-dominant colitis. These findings suggest clinical characteristics in this condition. Further assessment of clinical and endoscopic features in more cases is necessary for establishing diagnostic criteria and understanding underlying mechanisms in those cases where 5-ASA aggravates the colitis.
Colitis* ; Colitis, Ulcerative* ; Colonoscopy ; Diagnosis ; Fever ; Humans ; Hypersensitivity ; Inflammatory Bowel Diseases ; Medical Records ; Mesalamine* ; Phenotype ; Ulcer*

BACKGROUND/AIMS: Recent developments in analytical techniques including next-generation sequencing have clarified the correlation between intestinal microbiota and inflammatory bowel disease. Fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC) is proposed as a potential approach to resolving their dysbiosis; however, its safety and efficacy have not been confirmed. This single-arm, open-label, non-randomized study aimed to evaluate the safety and efficacy of FMT for Japanese patients with UC as the first registered clinical trial in Japan. METHODS: We enrolled 10 patients with active UC despite medical therapy. The donors were the patients' relatives and were carefully screened for infectious diseases. Fecal material was administered via colonoscopy, and the primary endpoint was the presence or absence of serious adverse events related to FMT. The secondary endpoint was a change in partial Mayo score at 12 weeks post-FMT. Scores ≤2 were considered a clinical response. Fecal samples were collected to follow changes in gut microbiota, while extracted complementary DNA were analyzed by a next-generation sequencer. We obtained written informed consent from all patients and donors. This study was approved by our Institutional Review Board and is registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN 000012814). RESULTS: Five patients with moderate disease and five with severe disease were enrolled. No severe adverse effects were observed. One patient achieved clinical response; however, none of the patients' microbiota diversity recovered to the donor levels. CONCLUSIONS: The use of single FMT for UC was safe; however, we failed to show its clinical efficacy and potential to change the intestinal microbiota.
Asian Continental Ancestry Group* ; Colitis, Ulcerative* ; Colonoscopy ; Communicable Diseases ; DNA, Complementary ; Dysbiosis ; Ethics Committees, Research ; Fecal Microbiota Transplantation* ; Gastrointestinal Microbiome* ; Humans ; Inflammatory Bowel Diseases ; Information Services ; Informed Consent ; Japan ; Microbiota ; Tissue Donors ; Treatment Outcome ; Ulcer*

Crude drugs that feature the name “gui” have appeared in classical medicinal textbooks with different names,and the correspondence between their names and origins remains the subject of research and discussion. In the present study, we investigated these correspondences using the descriptions in the annotations of the Bencaojingjizhu and through our previous study that revealed the standards of weights and measures in this book. Based on this investigation, we strongly speculate that “gui” in the Bencaojingjizhu was the branch skin of Cinnamomum cassia (C. cassia) (corresponding to cinnamon sticks in the market), which fits with the descriptions about the length and weight of “gui” -related crude drugs in this book. We measured the contents of cinnamic aldehyde and coumarin in the branch skin of C. cassia, and compared these to contents in other crude drugs related to “gui” that can be obtained on the market. The contents of these two compounds in the branch skin of C. cassia were similar to those in the bark of C. cassia from Vietnam that meets the standards for cinnamon bark in the Japanese Pharmacopoeia and is regarded as high-grade in the market. These results support our speculation, and it might be possible that the branch skin of C. cassia can be used as medicine instead of cinnamon bark.

The IPCD (Immersing Powdered Crude Drugs) method, inspired by the “zhu san fa” which was widely used in the Song period of China, has been developed to prepare Kampo decoctions quickly and easily, with highyield extract from crude drugs. One trouble with the IPCD method occurs when separating the decoction from the muddy residue of the crude drug powder. When powdered ephedra herb is packed in a nonwoven fabric bag and immersed in hot water, yield of the marker compounds is much lower than that obtained when ephedra herb powder is dispersed freely in hot water without a nonwoven fabric bag. Thus the use of a nonwoven fabric bag was shown to be unsuitable with the IPCD method. In investigating an easy and more efficient separation method, we tried decanting with a commercially available wine carafe to separate the decoction and residue. With IPCD followed by decantation using the wine carafe, yields of about 80% decoction volume were obtained as compared with those when cut crude drugs are decocted and filtered using a tea strainer, in 6 of the 7 formulas tried. We find that decantation using a wine carafe is a more practical way of separation in the IPCD method.

The incidence and prevalence of inflammatory bowel diseases (IBDs) including ulcerative colitis and Crohn disease are rapidly increasing in Western countries and in developed Asian countries. Although biologic agents targeting the immune system have been effective in patients with IBD, cessation of treatment leads to relapse in the majority of patients, suggesting that intrinsic immune dysregulation is an effect, not a cause, of IBD. Dramatic changes in the environment, resulting in the dysregulated composition of intestinal microbiota or dysbiosis, may be associated with the fundamental causes of IBD. Japan now has upgraded water supply and sewerage systems, as well as dietary habits and antibiotic overuse that are similar to such features found in developed Western countries. The purpose of this review article was to describe the association of diet, particularly Japanese food and microbiota, with IBD.
Animals ; *Asian Continental Ancestry Group ; Diet/*ethnology ; Evidence-Based Medicine ; Food Habits/ethnology ; Humans ; Incidence ; Inflammatory Bowel Diseases/diagnosis/diet therapy/*ethnology/immunology/*microbiology ; Intestines/immunology/*microbiology ; Japan/epidemiology ; *Microbiota ; Prevalence ; Probiotics/therapeutic use ; Prognosis ; Risk Factors