薬理と治療

Background Pharmaceutical intervention（prescription modification via prescription inquiries） by hospital pharmacists has been reported to improve the safety of pharmacotherapy. However, the reporting on pharmaceutical intervention by community pharmacists has been insufficient. Methods In this study, we analyzed cases of pharmaceutical intervention by community pharmacists（PREAVOID reports）collected by the Kurume Mii Pharmaceutical Association. Results In 67％ of the cases, the patients were≥60 years of age. The number of cases in which adverse drug reactions（ADRs）or the aggravation of ADRs was avoided was 287 and 10 respectively. Checking the medication notebook and the patientʼs medication history was helpful in 61％ of the cases in which ADRs were prevented. Consequently, patients could avoid contraindications from co-administration and duplicated administrations. Patients recovered from adverse events in pharmaceutical interventions in which patient symptoms and blood test results were studied. The estimated pay out for reactive relief systems for ADRs is approximately 1000 times higher than the additional dispensing fees associated with pharmaceutical interventions. Conclusions Risk evasion through these interventions by community pharmacists suppressed the development of side effects, avoided the recurrence of ADRs, and reducing exacerbation or worsening of primary disease. The economic impact was also high.

The present study analyzed the effect of increasing doses of DPP-4 inhibitor to discover the factors affecting the dosage increase of oral hypoglycemic agents to diabetic patients. The analysis objects were 737 cases stored in a DPC receipt database, who were separated into two groups that one group showed the effect of increasing doses while the other group did not. We analyzed the two groups separately and observed no significant differences due to the usage of concomitant medications. By the machine learning model constructed in this study, the training data showed a high precision with AUC higher than 0.8, whereas the test data showed a standard precision with AUC between 0.6 and 0.75. We calculated the top 10 feature values that affected this model greatly. The maximum value, the minimum value and the trend of HbAlc were included in the top 10 feature values collectively. Besides, the minimum value of glucose was also recognized as one of the top feature values tested by various cross validations. Some of the parameters of liver function, such as γ-GTP, AST, ALT and cholinesterase, were recognized as a feature value but they were inconsistent by different cross validations with the contribution left unclear. In the future, it is better to consider the necessities of securing a larger blood test result data number with fine granularity, and utilizing databases storing daily outpatient clinical data covering the states of chronic diseases. In addition, adoption of Dimensionality Reduction Techniques, such as input of compressed data to extract feature values more concisely, may also help to increase the property of feature value extraction. The new utilization of RWD is expected by solving the above issues.

Background S-flurbiprofen plaster（SFPP）is a newly developed tape-type patch of non-steroidal anti-inflammatory drugs（NSAIDs）, containing S-flurbiprofen （SFP）as an active ingredient. SFPP exhibits a significant clinical efficacy owing to the dramatically improved penetration of the active ingredient into deep tissues via good percutaneous absorption. The cardiovascular（CV）effects can be one of the class effects and they are worthy of attention. Therefore, we exploratory investigated the CV effect of SFPP, which results in comparable systemic exposure to that of oral flurbiprofen after long-term application in elderly patients with osteoarthritis. Methods A total of 201 patients with osteoarthritis（mean age, 66.3 years; 151 females）were treated with SFPP at 40 or 80 mg for 52 weeks. CV events observed after the application of SFPP were investigated. Results CV adverse events were observed in 4.5％（9╱201 patients）; however, none of them was classified as severe. Eight of the nine patients, who showed CV events, had CV diseases and╱or hypertension at baseline. Any causal relationship between SFPP and CV events was denied by investigators on the basis of the patientsʼ clinical courses. There was no relationship between CV events and plasma concentration of SFP in these patients. Conclusions Although CV events were observed in 4.5％ of the patients after the application of SFPP, no apparent causal relationship between SFPP and CV events was observed on the basis of the clinical course and plasma SFP concentration.

We investigated that influence of Kori-tofu on healing of skin wound by using a rat model of pressure injury. Pressure injury was induced experimentally on 9 weeks old SD rats. Low protein diet was fed with╱without 275 mg╱kg╱day of powdered Kori-tofu. Healing process was compared between the control group and the Kori-tofu intake group with“Daily wound area ratio”“, Integrated daily wound area ratio”and“Time taken to heal”. Healing of the Kori-tofu intake group was earlier than that of the control group. We conclude that intake of Kori-tofu promotes healing of pressure injury.

Objectives The aim of this study was to evaluate the effect of the ingested foods containing the green-tea polyphenol epigallocatechin gallate（EGCg）on dental plaque formation and adhesion. Methods A randomized placebo-controlled double-blind crossover study was carried out on 23 healthy, female university students（aged 20︱23 years, effectiveness analysis subject number: 20）. The study participants were forbidden from using toothbrushes, and at every meal they were instructed to ingest food containing 6 mg of EGCg. Results The status of plaque adhesion（plaque index）showed a significant improvement （P＜0.05）after three days. Conclusions In conclusion, EGCg-containing foods have an inhibitory effect on dental plaque formation and adhesion, and are suitable for individuals who are concerned about oral hygiene. This trial was registered at http://www.umin.ac.jp/ctr/ as UMIN000029694.

Objectives The aim of the present study was to investigate an effect of chocolate containing fructooligosaccharides on postprandial blood glucose in healthy human. Method Three randomized and crossover trials were conducted. Eleven subjects ingested a chocolate with（test diet）or without（control diet） fructooligosaccharides, and sucrose only. Blood glucose was measured before and 15, 30, 45, 60, 90, and 120 minutes after ingestion. Results Analysis of all subjects revealed no significant difference between the control and test diets. However, the test diet showed significant decrease in incremental area under the curve（ΔAUC）when compared with sucrose only while control diet did not change. Compared to sucrose only, the chocolate with or without fructooligosaccharides significantly decreased blood glucose and Cmax. Conclusions These results indicated that ingesting chocolate with or without fructooligosaccharides would elicit a significant lower blood glucose than sucrose alone. It seems likely that the chocolate with fructooligosaccharides may exhibit its hypoglycemic effects by decreasing the ΔAUC. （UMIN ID：UMIN000034606）

Objective The aim of the present study was to examine the efficacy of nobiletin contained in Shikwasa fruit juice drink for lowering serum uric acid level, as well as its safety, in healthy male adults with marginal hyperuricemia. Methods The study was a 8-week exploratory open-label clinical trial on male adults whose baseline serum uric acid levels were ranging between 7.0 and 8.9 mg╱dL. Twenty -one participants were assigned to receive a low-dose test drink（50 mL containing 25 mg nobiletin per day）or a high-dose test drink（100 mL containing 50 mg nobiletin per day）daily for 8 weeks. To evaluate the efficacy of the test drink consumption, serum uric acid level and excreted amount of uric acid in urine were determined at baseline and at weeks 4 and 8 in all participants. Results Analyses of the total efficacy-evaluable population（n＝10 each in both low-and high-dose groups）showed that the low-dose test drink intake virtually had no effect on the serum uric acid level throughout the treatment, whereas there was a trend for high-dose test drink intake to lower the serum uric acid level and a significant difference was observed at week 8 when compared with baseline. The test drink at both doses was well tolerated without any reported untoward side effects or laboratory abnormalities. Conclusion The results of the present study are the first finding that citrus nobiletin has the potential for safely lowering serum uric acid level in adult men with marginal hyperuricemia, suggesting the beneficial effect on hyperuricemia and related medical conditions. （UMIN︱CTR╱UMIN000028828）

Objectives The process of binding between a reducing sugar and protein is called glycation, and advanced glycation end products（AGEs）lead to the development of various diseases. As glycation occurs through an oxidation reaction, antioxidant-containing foods supposedly exert antiglycation effects. Hence, this study aims to investigate the antiglycation effect of Liquid of Fermented Plant Extract SW, a mix of fermented fruit and vegetables containing antioxidants. Methods We assessed the inhibition of the glyceraldehyde-AGEs production as antiglycation. We prepared aminoguanidine solution（0, 0.4, 2, and 10 mM）, Liquid of Fermented Plant Extract SW［0.0625％-50％（w╱v）］, ascorbic acid（0.16, 0.8, and 4 mM）, and acetylcysteine （0.16, 0.8, and 4 mM）. Results The production of glyceraldehyde︱AGEs was inhibited like the aminoguanidine result with 0.125％ （w╱v）or greater Liquid of Fermented Plant Extract SW. Moreover, ascorbic acid and acetylcysteine inhibited the production of glyceraldehyde－AGEs. However, the inhibitory action of Liquid of Fermented Plant Extract SW toward AGEs exhibited different behavior from ascorbic acid and acetylcysteine. Conclusions This study suggests that Liquid of Fermented Plant Extract SW blocks a reaction between glyceraldehyde and proteins, inhibiting the formation of glyceraldehyde-AGEs. Perhaps, Liquid of Fermented Plant Extract SW could inhibit the production of AGEs through a different pathway from ascorbic acid and acetylcysteine.

Objective To investigate the effect of Palatinose on concentration and attention, the present study was conducted on 40 healthy males and females. Method Subjects took the Cognitrax test（which evaluates neurocognitive function）at 60 min pre-ingestion, and 60, 120, and 180 min post-ingestion of 20 g of either Palatinose or glucose. Ten items were scored, including simple and sustained attention, and scores were compared. Result The test results showed that after ingestion of Palatinose, the scores were significantly higher at 60 and 180 min post-ingestion compared with scores after ingestion of glucose, indicating that Palatinose ingestion contributes to maintenance of simple attention for an extended period, and suppresses drowsiness after eating compared to glucose ingestion. The mechanism of action may be that Palatinose is more slowly digested than glucose, resulting in reduced blood glucose fluctuations. Conclusion The results of the present study demonstrated that Palatinose® ingestion helps to maintain attention and concentration, leading to accurate cognitive task responses for an extended period of time（. UMIN：000028929）

Aims To conduct an uncontrolled open-label study on healthy subjects to evaluate the safety of excessive consumption of saw palmetto oil at five times the recommended daily limit. Methods Five capsules containing 400 mg saw palmetto oil per capsule were consumed every day for 4 weeks by 22 subjects （11 males and 11 females; age 26-63 years）, followed by observations for body weight, BMI, blood pressure╱pulse, clinical examination, and adverse events. Results No significant changes were observed in the body weight and BMI in comparison with the pre-test values among the subjects. However, significant changes were observed for several specific tests within the clinical examinations, including hematology, blood biochemistry, endocrine, and urine test in comparison with the pre-test values, although no changes were considered to be clinically problematic from both clinical and physical examinations as well as no side-effects were observed. Conclusion The safety of excessive consumption of the experimental food was confirmed in this study, as it was observed to induce no side︱effects as well as any other events considered to be problematic in safety evaluation.（ UMIN 000033538）

Objectives The aim of this study is to evaluate for the effects of the supplement containing Andrographis paniculata（Burm. f.）Nees extract on subjects with high normal liver function. Methods A randomized, double-blind, placebo-controlled, parallel-group study was conducted. Forty-four subjects aged 20 to 64 years whose ALT levels were top 44 out of the participants applying to the criteria （both ALT and AST less than 50 U╱L）were randomly divided into two groups: the test product（supplement containing Andrographis paniculata extract）group and control product（placebo）group. The subjects were given each product for 12 wk. Daily intake of the test product was contained 700 mg of Andrographis paniculata extract. Markers of liver function, LPO and the safety were evaluated. Results Compared with placebo group, the test product group did not show any significant improvement on liver function and LPO. Conversely, markers of liver function indicated slight increase. Side effects related to the test product group were not confirmed in this study. Conclusions These results suggested that consecutive intake of 700 mg╱day of Andrographis paniculate extract for 12weeks had no positive effect on high normal liver function. （UMIN ID：UMIN000027495）

Objectives We aimed to determine whether the ingestion of acetic acid bacteria could reduce nasal discomfort. Methods We conducted a randomized double-blind placebo-controlled study. Eighty Japanese males and females（mean age：38.6 ±1.2 years）with complaints of daily nasal discomfort were randomly assigned to an acetic acid bacteria group or a control group. The subjects ingested acetic acid bacteria（4⊠1010 cells╱day）or placebo for 8 weeks. Nasal discomfort was evaluated using the Japanese Rhinoconjunctivitis Quality of Life Questionnaire at preingestion and at 4 and 8 weeks during the ingestion period. Results The acetic acid bacteria group had a significantly lower nasal discomfort score compared to the control group at 4 weeks after ingestion（P＜0.05）with no adverse effects observed. Conclusion Our findings suggest that the continuous ingestion of acetic acid bacteria relieves nasal discomfort（. UMIN000033383）

We evaluated the effects of Moringa oleifera Lamarck（moringa）leaf powder on defecation in healthy adult women with mild constipation. This randomized double-blind, placebo-controlled, crossover comparative study included volunteers, who were randomized into the moringa leaf powder capsule group（1.38 g of moringa leaf powder administered daily for 2 weeks） and placebo capsule group. In the evaluation of bowel habits, defecation frequency significantly increased during the ingestion period of moringa leaf powder compared with that during the placebo ingestion period. In addition, stool volume tended to increase during the moringa leaf powder ingestion period compared with the placebo ingestion period. These results suggest that moringa leaf powder intake might improve defecation in healthy adult women with mild constipation （.UMIN000024674）

Inulin-type-fructan has been known to have various functions as a prebiotic. Especially, the intestine regulating function has been many reported with a focus on bifidogenic effect and bowel habit. However, since previous studies have been conducted with high inulin intake, it was a factor in obstacles to the development of functional foods using inulin. The aim of this randomized, double-blind, placebo -controlled, cross-over trial was to determine the effect of low inulin intake on gut microbiota and bowel habit in thirty healthy Japanese adults. As a result of intake of green tea containing Fuji FF（5 g╱day）for 4 weeks, fecal bifidobacteria significantly increased（P＜0.05）. In addition, in the subject with constipation, the change in stool frequency and stool amount significantly increased（P＜0.05）. The present study revealed that relatively low inulin intake improved gut microbiota and bowel habit.

Objectives The purpose of this present study was to investigated effect of ginseng-containing tea intake on cognitive performance.（ UMIN000034367） Methods Subjects was 40 volunteers, aged between 13 and 18 years, were randomly allocated to either the placebo group, in which subjects consumed placebo tea, or the ginseng group, in which subjects consumed the ginseng-containing tea. The cognitive performances measured by Benton Visual Retention Test（BVRT）, Uchida︱Kraepelin psychodiagnostic test （UKT）and TK system Tanaka AB style intelligence test that before and after a 4 week. Results There was a significant interaction over 4 weeks in BVRT score and between the ginseng group and the placebo group. Conclusion These results suggest that Panax ginseng containing tea was beneficial in the visual cognitive performance improvement among adolescence.

Objective The aim of this study was to investigate the effect of a dietary supplement containing porcine skin collagen peptides on bone metabolism on healthy subjects. Methods A randomized, double-blind, placebo-controlled parallel-group, comparison study was conducted in 24 healthy subjects（50-72 years old）. The subjects were randomized into two groups and given either the test product（125 mL drink containing 10 g collagen peptides derived from porcine skin）per day or the control product（placebo drink）for 12 weeks. Serum and urinary biomarkers were evaluated for bone metabolism. Results The urinary biomarkers of bone metabolism were not significantly changed. However, the serum biomarker of bone metabolism（bone specific alkaline phosphatase（BAP））was significantly improved at 12 weeks in the test product group who took collagen peptides compared to the placebo group. Conclusions The results suggested that daily supplementation of collagen peptides derived from porcine skin might provide a beneficial effect on bone formation（. UMIN-CTR000033460）

Objectives This study aims to investigate the effects of intake of a dietary supplement containing bilberry extract on eye fatigue resulting from deterioration in accommodative function caused by visual display terminal（VDT）work in healthy Japanese subjects. Methods This randomized, double-blind, parallel-group, placebo-controlled study was conducted on 44 healthy Japanese subjects who were experiencing eye fatigue caused by VDT work. The subjects were randomly assigned to either supplement with bilberry extract （BB group, n＝22） or placebo（P group, n＝22）group using a computerized random number generator, and each subject took one capsule per day for 12 weeks. Assessments of accommodative function and night vision and questionnaires were completed before intake and at 4, 8, and 12 weeks after intake. Safety evaluation was performed via ophthalmic examination. Somatometric parameters, physical examination, urinalysis, and blood tests were conducted before intake only. Results The final analysis included 17 subjects in the BB group and 18 subjects in the P group. The BB group had significantly higher pupillary constriction ratios, which were adjusted by calculating load in the dominant eye and both eyes, compared with the P group （P＝0.039 and P＝0.026, respectively）. No safety concerns were noted. Conclusions The consumption of a supplement containing bilberry extract for 12 weeks improved accommodative function, eye fatigue, and subjective eye-related symptoms. In the BB group, the decline in accommodative function caused by VDT work improved over the 12 weeks, subjective symptoms were alleviated, and eye fatigue was temporarily reduced. Trial registration UMIN-CTR: UMIN000029213Funding YAWATA CORPORATION

Objective The aim of the present study was to examine whether the intake of a single drink containing psicose（allulose）affects fat oxidation in healthy adults during exercise. Methods A randomized, double-blind, placebo-controlled, cross-over trial was conducted for 48 healthy male subjects aged from 20 to less than 40 years old. After overnight fasting, the subjects ingested a water drink containing 5 g of psicose or an identical tasting placebo drink not containing psicose 30 min before exercising. An ergometer was used for 60 min of exercise and the exercise intensity was set to moderate based on the 60％ ventilation threshold（60％ VT）for each subject. Indirect calorimetry was performed during exercise to measure the VO2 and VCO2 to calculate fat oxidation, carbohydrate oxidation, and energy expenditure. Results The psicose drink significantly increased the incremental area under the curve（ΔAUC）for fat oxidation and decreased the ΔAUC for carbohydrate oxidation during exercise from 10 to 60 min compared with the placebo. There was no significant difference in energy expenditure, and no adverse effects were observed with either drink. Conclusions The intake of a single psicose-containing drink increased fat oxidation during moderate exercise, suggesting that fat was preferentially utilized as an energy substrate instead of carbohydrates. Thus, psicose may enhance fat oxidation during exercise, and may be added to foods to prevent the development of obesity and to maintain general health. （UMIN︱CTR ID: UMIN000033260）

Objectives This study investigated the effects of foods containing aged garlic extract on fatigue and quality of sleep. Methods This randomized, double-blind, placebo-controlled parallel study included 29 healthy volunteers （12 males, 17 females）who consumed a placebo or test food for twelve weeks. Subjective mood （fatigue, quality of sleep）was evaluated using the visual analogue scale（VAS）, and the OSA sleep inventory MA version（OSA-MA）was administered. Serum superoxide dismutase and glutathione peroxidase（GPx）levels and urinary isoprostane levels were measured. Results Significant differences between the test and placebo groups were observed for the VAS scores for fatigue and quality of sleep. The VAS score for fatigue was significantly decreased after twelve weeks of test food intake. The VAS score of quality of sleep was significantly elevated after twelve weeks of test food intake. The total OSA-MA score, the score for sleepiness at rising, sleep onset-sleep maintenance, and fatigue recovery were elevated. Serum GPx levels in the test food group were significantly higher than those in the placebo group after twelve weeks. Urinary isoprostane levels in the test food group were significantly lower than those in the placebo group after twelve weeks. Conclusions Foods containing aged garlic extract can decrease fatigue and improve quality of sleep. There is the possibility that the mechanism of action is improved antioxidant activity in the body. Trial registration UMIN-CTR: UMIN000029107