Saireito (TJ-114), a Japanese traditional herbal medicine, reduces 5-fluorouracil-induced intestinal mucositis in mice by inhibiting cytokine-mediated apoptosis in intestinal crypt cells.

Clinical chemotherapy frequently causes intestinal mucositis as a side effect, which is accompanied by severe diarrhea. We recently showed that the cytokine-mediated apoptotic pathway might be important for the development of intestinal mucositis induced by 5-fluorouracil (5-FU). Saireito, the traditional Japanese herbal (Kampo) medicine, is widely used to treat diarrhea and various inflammatory diseases in Japan. In the present study, we investigated the effect of saireito on 5-FU-induced intestinal mucositis in mice, especially in relation to apoptosis in the intestinal crypt. Male C57BL/6 mice were given 5-FU (50 mg/kg), i.p. once daily for 6 days. Intestinal mucositis was evaluated histochemically. Saireito (100-1000 mg/kg) was administered p.o. twice daily for 6 days. Repeated 5-FU treatment caused severe intestinal mucositis including morphological damage, which was accompanied by body weight loss and diarrhea. Daily administration of saireito reduced the severity of intestinal mucositis in a dose-dependent manner. Body weight loss and diarrhea during 5-FU treatment were also significantly attenuated by saireito administration. The number of apoptotic and caspase-3-activated cells in the intestinal crypt was increased, and was accompanied by up-regulated tumor necrosis factor (TNF)-α and interleukin (IL)-1β mRNA within 24 h of the first 5-FU injection. However, all of these measures were significantly lower after saireito administration. These results suggest that saireito attenuates 5-FU-induced intestinal mucositis. This action may come from the reduction of apoptosis in the intestinal crypt via suppression of the up-regulation of inflammatory cytokines. Therefore, saireito may be clinically useful for the prevention of intestinal mucositis during cancer chemotherapy

Effect of saireito on the anti-tumor action, body weight loss, and diarrhea induced during 5-fluorouracil (5-FU) treatment in Colon 38 tumor-implanted mice.

<p>5-FU (20 mg/kg) was injected i.p. once daily for 6 days (days 7–12), while saireito (1000 mg/kg) was administered p.o. twice daily for 14 days (days 7–21), starting 7 day after tumor implantation. The volume (mm³) of solid tumor (A), body weight (B), and diarrhea score (C) were determined every 2 or 3 days, starting 7 days after the implantation. Data are presented as the mean ± SEM of 6–8 mice. *<i>P < 0.05</i>, versus control (vehicle alone); ^#<i>P < 0.05</i>, versus normal (5-FU-untreated).</p

Effect of saireito on apoptosis and caspase-3 activation in the intestinal crypt induced by 5-fluorouracil (5-FU).

<p>5-FU (50 mg/kg) was injected i.p. while saireito (1000 mg/kg) was administered p.o. twice, 30 min before and 8 h after 5-FU injection. The jejunum was excised 24 h after 5-FU injection, sectioned, and TUNEL assay (A, 400×) and cleaved-caspases-3 immunostaining (B, 400×) were performed. The number of apoptotic (C) and caspase-3-activated cells (D) were counted. Data are presented as the mean ± SEM of 6 mice. *<i>P < 0.05</i>, versus control (vehicle alone); ^#<i>P < 0.05</i>, versus normal (5-FU-untreated).</p

Three-dimensional high-performance liquid chromatograph pattern of saireito (TJ-114).

<p>Three-dimensional high-performance liquid chromatograph pattern of saireito (TJ-114).</p

Effect of saireito and daikenchuto on changes in body weight and diarrhea during 5-fluorouracil (5-FU) treatment.

<p>5-FU (50 mg/kg) was injected i.p. once daily while saireito (100–1000 mg/kg) and daikenchuto (2700 mg/kg) were administered p.o. twice daily for 6 days (days 0–5). Body weight is shown as a percentage of initial body weight (A), whereas the severity of diarrhea is scored using the four-grade scale (0 to 3) (B). Data are presented as the mean ± SEM of 6–8 mice. *<i>P < 0.05</i> versus control (vehicle alone), ^#<i>P < 0.05</i> versus normal (5-FU-untreated).</p

Start and initial results of the fukushima prefecture acute myocardial infarction registration survey

Acute myocardial infarction (AMI) remains one of the most serious heart diseases and elucidation of its pathogenesis and advances in treatment strategies have been desired. In 2009, to understand the status of AMI in Fukushima Prefecture for improving treatment outcomes, a new AMI registration survey system was conducted throughout the prefecture. A total of 1,556 cases were registered in the initial 2 years from 2009 to 2010. The hospital-based overall incidence of AMI in Fukushima Prefecture was 37.9 people per population of 100,000 per year. Mortality from AMI within 30 days of onset was 10.2%. We report herein the actual situation of AMI onset and treatment in Fukushima Prefecture based on the initial results of the survey

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to &lt; 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of &amp; GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P &lt; 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo