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Background: We investigated the extent of growth of microorganisms with simultaneous administration of lipid emulsions with infusions for Total Parenteral Nutrition (TPN), assuming that the lipid emulsions contaminated with microorganisms are stagnant in a closed-type infusion device. We also investigated if bacterial growth can be prevented in the infusion device by flushing the inside of the infusion device with saline solution after the administration of lipid emulsion from the side tube in vitro setting. Methods: We made a preparation by adding Escherichia coli to the lipid emulsion and started the infusion simultaneously with the infusion solution for TPN and lipid emulsion with the piggyback method. Immediately after the completion of lipid emulsion infusion, we conducted flushing with saline solution. The volume of saline solution was none, 5, 10, or 20 mL at a flow rate of 1 mL/s. Infusion solution that was stagnant in the infusion device was collected immediately before completing the lipid emulsion infusion and 20 h after flushing, i.e., 24 h after starting the infusion for TPN, and the number of viable bacteria was determined. Results: The number of viable E. coli increased in the infusion device of all three species used in this experiment 24 h after starting the lipid emulsion infusion without flushing. We found that bacterial growth could be prevented through flushing with saline solution after the completion of lipid emulsion infusion and flushing out the stagnant infusion solution in the closed-type infusion device. Conclusions: We found that if E. coli was present in the closed-type infusion device, it would multiply. We also found that the number of viable bacteria varied according to the variety and internal structure of the closed-type infusion device as well as the liquid volume used for flushing, although flushing can prevent the growth of microorganisms. Proper management and manipulation of infusion is required to prevent infection.

Deterioration of drugs due to light exposure is one of the major concerns, especially regarding protection of high-calorie infusion solutions, lightproof covers are used in hospitals. In the absence of any set standards regarding their usage, they are often reused. This study aimed to investigate bacterial contamination of lightproof covers used in hospital wards. For this, lightproof covers which had been used or stored in wards were collected and bacterial cultures were carried out from them. Examination of the cultures revealed that bacteria were present in the used lightproof covers. The bacterial species detected in the used lightproof covers were Bacillus species Coagulase-negative Staphylococci (CNS) and Methicillin-resistant Staphylococcus aureus (MRSA). Bacillus species and CNS were also detected in lightproof covers stored in wards, whereas MRSA was not detected. Intestinal bacteria were detected in only one lightproof cover. However, no bacteria were detected from either inside or outside of the unused lightproof covers that were stored in the drugs department. After allowing the unused lightproof covers stored in the drugs department to stand for 24 h, Bacillus species and CNS were detected in only one of the covers, whereas no bacteria was detected in other covers. These results indicate that there is a risk of bacterial contamination in the reuse of lightproof covers and that they should either be disposed off properly after usage or hand, finger disinfectants should be used while handling them to prevent any possible contamination.

BackgroundThe use of enteral nutrients plays a highly important role in accurate nutrition management, but limited information is currently available on the cautionary points of semi-solid enteral nutrients.AimIn this study, we examined whether the pharmacokinetic profiles of sodium valproate (SVA), levetiracetam (LEV), and carbamazepine (CBZ) are affected by altering the dosing time of RACOL®-NF Semi Solid for Enteral Use (RASS), a prescribed semi-solid formula. We also investigated whether the pharmacokinetic interaction observed in this study can be avoided by staggered dosing of the chemical drug and semi-solid enteral nutrient.MethodsThe plasma concentration of SVA, LEV and CBZ after oral administration was measured by LC-MS/MS method.ResultsThere was no difference in pharmacokinetic characteristics of SVA and LEV when the dosing time of RASS was altered. On the other hand, the plasma concentration of CBZ after oral administration at all sampling points decreased with the extension of the dosing time of RASS, which was consistent with the Cmaxand AUC. However, no significant difference was observed in the pharmacokinetic profiles or parameters of CBZ between the short-term and long-term RASS dosing groups by prolonging the administered interval of CBZ and RASS for 2 hr.ConclusionWe concluded that the pharmacokinetic profiles of CBZ, but not SVA and LEV, after its oral administration are affected by the dosing time of RASS, but staggered administration of CBZ and RASS prevented their interaction.

WHAT IS KNOWN AND OBJECTIVE Though most medical institutions calculate antimicrobial susceptibility and resistance rates of microbes isolated at their own facility as part of their efforts to promote the proper use of antibiotics, very few, if any, regularly monitor cross-resistance rates between antimicrobial agents. The authors have devised a tool in the form of a cross-resistance rate correlation diagram (CRR diagram) that allows easy identification of increases or decreases in, or changes in the pattern of, antimicrobial cross-resistance. The objective was to perform an analysis by CRR diagrams of the effect of relocation to a newly built facility on antimicrobial resistance and cross-resistance rates at a medical facility. METHODS The Sakai City Medical Center relocated in July 2015 to a newly built facility located in a different primary medical care zone 3.5 km away. Based on the drug susceptibility test data compiled at the Sakai City Medical Center, resistance and cross-resistance rates of Pseudomonas aeruginosa before and after the relocation of the hospital facility were calculated, and the rates were assessed using CRR diagrams. RESULTS AND DISCUSSION It was possible to confirm the effect of hospital relocation on antibiotic susceptibility of P aeruginosa in terms of changes in resistance and cross-resistance rates. The effect of the facility's relocation on cross-resistance rates was particularly notable with respect to β-lactam antibiotics: cross-resistance rates among β-lactams decreased substantially, represented as a large wedge-shaped change towards the origin on the CRR diagram. Rates of cross-resistance between classes of antibiotics with a different mechanism of antibiotic action changed little. WHAT IS NEW AND CONCLUSION Including cross-resistance rates in the routine monitoring of resistance and susceptibility rates practiced by a medical institution can provide a comprehensive insight into the dynamics of bacterial flora in the facility. CRR diagrams, which allow visualization of the status and changes in cross-resistance, not only provide a new perspective for clinicians, but they also contribute to the proper use of antibiotics and serve as a tool in the education of healthcare professionals and students about antibiotic resistance.

BackgroundTo support effective antibiotic selection in empirical treatments, infection control interventions, and antimicrobial resistance containment strategies, many medical institutions collect antimicrobial susceptibility test data conducted at their facilities to prepare cumulative antibiograms.AimTo evaluate how the setpoints of duplicate isolate removal period and data collection period affect the calculated susceptibility rates in antibiograms.MethodsThe Sakai City Medical Center is a regional core hospital for tertiary emergency medical care with 480 beds for general clinical care. In this study, all the Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae isolates collected at the Sakai City Medical Center Clinical Laboratory between July 2013 and December 2018 were subjected to antimicrobial susceptibility tests and the resulting data was analyzed.FindingsThe longer the duplicate isolate removal period, the fewer the isolates are available for every bacterial species. Differences in the length of the duplicate isolate removal period affected P. aeruginosa susceptibility rates to β-lactam antibiotics by up to 10.8%. The setpoint of the data collection period affected the antimicrobial susceptibility rates by up to 7.3%. We found that a significant change in susceptibility could be missed depending on the setting of the data collection period, in preparing antibiogram of β-lactam antibiotics for P. aeruginosa.ConclusionsWhen referring to antibiograms, medical professionals involved in infectious disease treatment should be aware that the parameter values, such as the duplicate isolate removal period and the data collection period, affect P. aeruginosa susceptibility rates especially to β-lactam antibiotics. And antibiogram should be updated within the shortest time period that is practically possible, taking into account restrictions such as numbers of specimen.

The use of semi-solid enteral nutrients plays an extremely important role in accurate nutrition management. In the present study, we compared the pharmacokinetic profile of orally administered carbamazepine (CBZ) in rats treated with liquid RACOL®, semi-solid RACOL®, and HINE E-gel®, which are enteral nutrients marketed in Japan. Since liquid and semi-solid formulations are both marketed in Japan for RACOL®, liquid RACOL® was orally administered to control rats. The serum concentration of CBZ at each sampling point was lower in the semi-solid RACOL®-treated group than in the liquid RACOL®-treated group. No significant differences were observed in the pharmacokinetic behavior of CBZ between the semi-solid RACOL®-treated and HINE E-gel®-treated groups. Regarding pharmacokinetic parameters, the impact of the area under the curve (AUC0→5h) was the liquid RACOL® group > the semi-solid RACOL® group ≈ the HINE E-gel® group. Therefore, we concluded that serum concentrations of CBZ were lower when concurrently treating with semi-solid enteral nutrients than when simultaneously processing liquid enteral nutrients.

Background Interferon and ribavirin have been used as therapeutic agents for chronic hepatitis C infection or C-compensated cirrhosis in the conventional treatment. Hepatitis C virus (HCV) -specific direct-acting antiviral agents that directly inhibit the growth process of HCV have been approved since 2011. However, in the early post-marketing vigilance phase of ledipasvir acetonate/sofosbuvir (LDV/SOF), there were reports of interstitial lung disease in 4 out of 32,700 cases with death in 1 case; the onset mechanism is unknown. Case presentation Treatment for hepatitis C was deemed to be necessary, and the patient was referred to our hospital. Oral administration of LDV/SOF was started. On day 8 of administration, a fever of 38–39 °C and coughing were observed followed by the gradual appearance of shortness of breath. As there was no improvement, the patient visited her primary care physician on day 16 of administration and the patient was brought urgently to our hospital on the same day. Blood tests and imaging tests were conducted at our hospital on the day of emergency transport; inflammatory response markers showed abnormal values, and sialylated carbohydrate antigen Krebs von den Lungen-6 was within the normal value range at 303 U/mL. Because the possibility of infection was low based on results of imaging and bronchoalveolar lavage, drug-induced lung disease was suspected, LDV/SOF administration was discontinued, and steroid administration was started. Following steroid pulse therapy, treatment with oral prednisolone tablets was gradually tapered. The patient’s symptoms were relieved and she was discharged. Conclusions The patient’s medication history in this case indicated that there were no drugs taken before or after administration of LDV/SOF until the adverse reaction occurred, and there were no supplements or dietary supplements taken. Therefore, LDV/SOF has been proposed as the cause of the suspected adverse effect. Pharmacists should try to collect adverse effect reports to identify adverse effects early.

Doxorubicin (DOX) is a highly potent anti-neoplastic agent widely used in clinical practice, but its dosage and duration of administration are strictly limited due to dose-related organ damage. In the present study, we examined whether theanine, an amino acid derivative found in green tea leaves, can protect against DOX-induced acute nephrotoxicity in rats. Decreases in the creatinine clearance by DOX administration were attenuated by concurrent treatment with theanine, which was consistent with the change in histological renal images assessed by microscopic examination. Theanine had no effect on the distribution of DOX to the kidney. The production of lipid peroxide in the kidney after DOX administration was suppressed by concurrent treatment with theanine. Reduced glutathione content, but not superoxide dismutase activity, was decreased following DOX administration, whereas this change was suppressed when theanine was given in combination with DOX. These results suggest that theanine prevents DOX-induced acute nephrotoxicity through its antioxidant properties.

Background Menthol is widely used as a constituent of functional foods and chemical drugs. In the present study, we investigated changes in the expression of cytochrome P450 isoform CYP3A4mRNA after treating human hepatocellular carcinoma HepG2 cells with menthol. We also examined the effects of pretreatment with menthol on the cytotoxic activity of paclitaxel (PAC) and vincristine (VIN), which are substrates of CYP3A4, in the cells. Methods HepG2 cells were maintained in Dulbecco’s Modified Eagle’s Medium. Expression of CYP3A4 was examined by the real-time polymerase chain reaction. Survival rate of HepG2 cells was evaluated by the MTT assay. Results The gene expression level of CYP3A4 in HepG2 cells was significantly reduced by treatment with menthol for 1 day. The viability of HepG2 cells was not affected by treatment with menthol alone once a day for two consecutive days. The degree of reduction in cell viability by PAC or VIN in HepG2 cells was significantly increased by menthol treatment for 24 h prior to exposure to these anti-cancer drugs. Conclusions These results demonstrate that menthol enhanced the anti-tumor effects of PAC and VIN through the downregulation of CYP3A4 in HepG2 cells without exerting cytotoxic activity.

1. We investigated the change in the pharmacokinetic profile of tolbutamide (TB), a substrate for CYP2C6/11, 4 days after single administration of 5-fluorouracil (5-FU), and the hepatic gene expression and activity of CYP2C6/11 were also examined in 5-FU-pretreated rats. 2. Regarding the pharmacokinetic parameters of the 5-FU group, the area under the curve (AUC) was significantly increased, and correspondingly, the elimination rate constant at the terminal phase (ke) was significantly decreased without significant change in the volume of distribution at the steady state (Vdss). 3. The metabolic production of 4-hydroxylated TB in hepatic microsomes was significantly reduced by the administration of 5-FU. 4. The expression level of mRNAs for hepatic CYP2C6 and CYP2C11 was significantly lower than in the control group when the rats were pretreated with 5-FU. 5. These results demonstrated that the pharmacokinetic profile of TB was altered by the treatment with 5-FU through a metabolic process, which may be responsible for the decreased CYP2C6/11 expression at mRNA levels.

Peripheral parenteral nutrition (PPN) solutions contain amino acids, glucose, and electrolytes, with or without some water soluble vitamins. Peripheral venous catheters are one of the causes of catheter related blood stream infection (CRBSI), which requires infection control. In Japan, PPN solutions have rarely been prepared under aseptic conditions. However, in recent years, the necessity of adding vitamins to infusions has been reported. Therefore, we investigated the effects of water soluble vitamins on growth of microorganisms in PPN solutions. AMINOFLUID® (AF), BFLUID® (BF), PARESAFE® (PS) and PAREPLUS® (PP) PPN solutions were used. Water soluble vitamins contained in PP were also used. Causative microorganisms of CRBSI were used. Staphylococcus epidermidis decreased after 24 hours or 48 hours in all solutions. On the other hand, Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans increased, especially in PP. When each water soluble vitamin was added to BF and PS, growth of S. aureus was greater in solutions that contained nicotinamide than in solutions that contained other vitamins. As for C. albicans, they grew in all test solutions. C. albicans grew especially well in solutions that contained biotin. When commercial amino acids and glucose solutions with electrolytes are administered, in particular those containing multivitamins or water soluble vitamins, efforts to control infection must be taken to prevent proliferation of microorganisms.

Objective: A palliative care knowledge survey was conducted involving pharmacy students to examine their perceived usefulness and the educational effect of clinical training in hospitals. Methods: A questionnaire sheet was distributed to fifth-year pharmacy students before and after clinical training. The questionnaire consisted of questions to clarify the details of palliative care-related training in hospitals and students’ knowledge of such care. The respondents were divided into 2 groups: those who participated in palliative care team (PCT) rounds (group A: 57) and those who did not (group B: 57). Results: The mean total correct answer rate markedly increased after training in group A, from 37.9 to 47.1% (P < .01). Such an increase was also observed in the domains of philosophy and pain in this group ( P < .01). In contrast, group B did not show differences in the mean correct answer rate between before and after training; there was no significant increase in the rate in any domain. Conclusion: Pharmacy students’ knowledge was enhanced by participating in the PCT, confirming the usefulness of such participation during training as part of palliative care education.

Objective The use of enteral nutrients plays an extremely important role in accurate nutrition management. Sodium alginate (SA) is frequently used for the semi-solidification of enteral nutrients. In the present study, we investigated whether the pharmacokinetic profile of orally administered carbamazepine (CBZ) is altered by a treatment with SA immediately before and after dosing of the drug. Furthermore, the adsorption effects of SA on CBZ were examined using an in vitro analysis. Method SA was orally administered to rats just before and immediately after CBZ dosing. The CBZ concentration profile following its oral administration was analyzed by a non-compartmental method. The adsorption of CBZ onto SA was evaluated after centrifugation using an ultrafiltration device. Findings The serum concentration of orally administered CBZ at each sampling point was reduced by the treatment with SA, and the extent of the decrease observed in the concentration of CBZ was larger when SA was ingested immediately after administration of the drug, which was consistent with the alteration observed in the value of the area under the curve (AUC). No significant differences were noted in the elimination rate at the terminal phase (ke) among the groups. In the in vitro assay, CBZ was adsorbed by SA in the solution used to reflect fluid in the intestinal tract. Conclusions The pharmacological efficacies of CBZ might be reduced by SA through the pharmacokinetic interactions, and that the careful attention should be paid to the timing of administration of CBZ and semi-solid enteral nutrients.

Background: The Guidelines for Parenteral and Enteral Nutrition in Japan state that parenteral fat emulsion can be infused through a secondary administration set. We tested the compatibility of fat emulsion with antibiotics in piggyback infusions in terms of changes in the size distribution of fat particles. Methods: Test mixtures of 5% glucose solution, fat emulsion, and 25 antibiotic agents were prepared in the ratio appropriate for piggyback infusion (33: 10: 40) and analyzed serially for the number of fine particles by size using a light-shielded automatic fine particle counter. Results: No marked changes were observed in the 12 β-lactam antibacterial drugs, clindamycin phosphate, teicoplanin, trimethoprim/sulfamethoxazole, and micafungin sodium even at 24 h after preparation. The particle size in the mixture containing vancomycin hydrochloride, levofloxacin hydrate, metronidazole, and fluconazole gradually increased after preparation. The particle size in the mixture containing gentamicin sulfate, arbekacin sulfate, minocycline hydrochloride, ciprofloxacin, and fosfomycin sodium changed significantly after preparation. Conclusions: The changes in the particle size observed with some drugs suggest that they may cause changes in the lipid particle size during administration and, therefore, those antibiotics agents should not be administered concurrently with fat emulsion.

Objective The management of nutrition using semisolid enteral nutrients is considered useful for avoiding the adverse effects associated with liquid enteral nutrients. In the present study, we used an in vitro analysis to investigate whether carbamazepine (CBZ) is adsorbed by the fibers included in semisolid enteral nutrients. The effects of these fibers on the pharmacokinetic profile of CBZ following its oral administration were also examined in rats. Methods The adsorption of CBZ onto fibers was examined by absorbance monitoring of the filtrate after centrifugation using an ultrafiltration device. Viscosities of each solution were measured by rotational viscosimeter. The CBZ concentration profile after its oral administration (50 mg/kg) was analyzed by a noncompartmental method. Results In the two solutions used to reflect gastric juice and fluid in the intestinal tract, CBZ was more strongly adsorbed by water-soluble fibers (guar gum and xanthan gum) than by insoluble fibers (dextrin hydrate). The adsorption of CBZ also was observed even if the concentrations of guar gum and xanthan gum were reduced to such an extent that viscosity was 0 Pa･s. The pharmacokinetic examination of orally administered CBZ revealed that the area under the curve was significantly lower in the guar gum and xanthan gum groups than in the control group. Conclusion CBZ was adsorbed by fibers used for the semisolidification of enteral nutrients, which may be partially responsible for the alterations observed in the pharmacokinetic profile of CBZ.

We investigated the effects of a Chinese herbal medicine, Gosha-jinki-gan (GJG), on the regulation of insulin levels in rats fed a sucrose-rich diet (SRD). Normal Wistar rats in the SRD group were fed an SRD for 4 weeks. Increased dietary sucrose did not alter plasma glucose levels but it increased plasma insulin levels at 2 and 4 weeks in the SRD-fed rats relative to control rats that were fed standard chow. GJG treatment significantly suppressed the SRD-induced elevation in plasma insulin levels. These results suggest that GJG improves hyperinsulinemia caused by an SRD.

A questionnaire was conducted among pharmacists working for 193 pharmacies regarding the present situation and their recognition of palliative treatment and narcotic analgesics.Responses to the questionnaire were collected from 171 pharmacists at 81 pharmacies,revealing that 70.2% of the pharmacists had experience of dispensing narcotic analgesics,46.8% of the pharmacies had a regular stock of narcotic analgesics,the mean number of narcotic items in stock was 6.5,and 25.3% of the pharmacies practiced home-visit treatment.The level of understanding palliative treatment and the proper use of narcotic analgesics was higher in pharmacists working for pharmacies dealing with narcotic analgesics,and engaged in homevisit activities than in those working in other situations.While many pharmacists gave instructions regarding adverse reactions to narcotic analgesics and precautions for their use to patients notified of their condition,they often only gave information on common indications and side effectsto patients yet to be notified or unaware of their condition.In the future,we should hold study meetings in communities to improve their expertise in palliative treatment.

Peptide YY (PYY) is produced by endocrine cells in the lower gastrointestinal tract. The main functions of PYY are antisecretory effects in the colon and inhibition of gastrointestinal motility. We chose PYY as an index of the intrinsic factor in diarrhea and examined the influence of changes induced in a diarrhea rat model by administration of 4 types of laxative and loperamide hydrochloride (loperamide) as an agent for the treatment of diarrhea. A specific radioimmunoassay was performed to determine plasma and intestinal mucosal PYY concentrations. PYY in the rat intestinal tissue extract was distributed at a high density in the lower intestinal mucosa. In the diarrhea rat model, multiple changes in PYY concentrations in the intestinal mucosa and plasma were observed. In rats administered castor oil and sodium picosulfate, the intestinal mucosal PYY levels significantly decreased in a dose-dependent manner. Plasma PYY levels significantly decreased only in rats administered magnesium citrate. Next, we examined the influence of loperamide administration on the intestinal mucosa and plasma PYY concentrations in these rats. Loperamide administration resulted in multiple changes in plasma and intestinal mucosa PYY concentrations, along with an improvement in the diarrhea. Our research showed that the endocrine hormone PYY is involved in the onset of diarrhea, the course of the condition, and the manifestation of medicinal effects in the lower intestine.

Indirect evidence suggests that lactoferrin (Lf), a major iron-binding protein in human milk, induces enterocyte growth and proliferation, depending on its concentration and affects the function and permeability of the intestinal mucosa. The bacterial endotoxin (lipopolysaccharide, LPS) is known to cause mucosal hyperpermeability in vivo. However, protective effects of Lf against LPS-mediated intestinal mucosal damage and barrier function in epithelial cells are not yet fully clarified. The aim of this study was to investigate whether Lf can reduce the cellular injury and alter epithelial hyperpermeability caused by LPS in human intestinal Caco-2 cells. When cell viability was measured by a WST-1 assay (tetrazolium salt-based assay), the protective effects against LPS-induced damage to Caco-2 cells were observed at doses of 800 and 1000 microg/ml Lf. The barrier function of Caco-2 monolayer tight junctions was assessed by measuring transepithelial electrical resistance (TEER) and permeability of FITC-labeled dextran 4000 (FD-4). The treatment of Caco-2 cells with Lf at doses of 400 and 1000 microg/ml significantly increased TEER as compared to treatment with LPS alone for 2 h (p

Few studies have reported the changes in the peptide YY (PYY) levels in the intestinal tissue of rats with ulcerative colitis (UC) following oral administration of mesalazine and prednisolone. We investigated the effects of these drugs on the intestinal mucosal PYY levels in a rat model of UC. We confirmed that the PYY levels in the rat intestinal mucosal tissue were high in the lower intestinal tract. The leukocyte count and hemoglobin levels approached the normal values after administering mesalazine or prednisolone to rats treated with 3% dextran sulfate sodium (DSS). The PYY levels in the caecum and colon decreased significantly after administering DSS but increased when mesalazine was administered in a tissue-specific manner. Unlike mesalazine, the PYY levels increased in the ileum in addition to the colon and rectum after administering prednisolone. However, neither of the drugs induced any changes in the plasma PYY levels. These findings indicate that changes in the intestinal tissue PYY levels may be partially involved in the improvement of DSS-induced UC in rats following the administration of these drugs.

Despite an increase in the number of reports on medical safety interventions conducted by ward-based pharmacists, only a few reports have classified intervention cases in detail. We classified and compared the types of medical safety intervention conducted by ward-based pharmacists since the introduction of their services. The interventions were classified into: cases that were identified by pharmacists or through asking questions about physicians' prescriptions before dispensing medications (active interventions); and those in which pharmacy technicians could contribute to medical safety by receiving inquiries from patients or healthcare providers (passive interventions). The numbers of the two types of intervention were compared. The number of interventions significantly increased after the introduction of ward-based clinical pharmacy services. Especially, the numbers of cases identified during ward rounds conducted by ward-based pharmacists (active interventions) and those identified by receiving inquiries from physicians or nurses (passive interventions) significantly increased, possibly because the collection of patient information was performed more efficiently by conducting ward rounds, and an environment where physicians and nurses can easily make inquiries to pharmacists was established after increasing the time pharmacists spend on hospital wards. The results demonstrate that the introduction of ward-based clinical pharmacy services has improved communication with patients, facilitated information-sharing among physicians, nurses, and other healthcare providers, contributed to the safer management of pharmaceutical operations, and increased interest of patients.

We investigated the ability of eicosapentaenoic acid (EPA) to prevent high-fat diet (HFD)-induced obesity and non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed standard chow (5.3% fat content), an HFD (32.0% fat content) or an HFD + EPA (1 g/kg/day EPA for the last 6 weeks) for 12 weeks. Serum total cholesterol, hepatic triglyceride and total cholesterol levels were significantly increased in the HFD group, in comparison with those of normal mice (p

At the Municipal Ikeda Hospital, a system in which pharmacists stationed in one ward pharmacy dispense drugs to be administered by injection and injectable preparations delivered to patients' bedsides was introduced in April 2000. This system was aimed at minimizing risks related to injections. Initially, however, on holidays, nurses played the roles of pharmacists in terms of the injections, and there were concerns over a possible rise in the incidence of errors (adverse events/near-misses) related to injections on these days compared with weekdays. Later, when planning to introduce a new holiday work system in the ward pharmacy, we took into account such factors as the number of pharmacists needed on holidays, their duties on holidays and the influence on weekday pharmacy activity of compensatory days-off taken by such pharmacists. In May 2004, the new holiday work system was introduced in the ward pharmacy. Under the new system, 5 pharmacists work at the ward pharmacy on holidays. After this system was put into operation, the number of injections dispensed at the ward pharmacy averaged 230 per day, and 177 per holiday. To evaluate the validity of this system, we recently conducted a questionnaire survey of nurses at our hospital. The survey involved 139 nurses. Of these nurses, 69.1% responded that the number of incidents (adverse events/near-misses) related to dispensing injections on holidays had decreased. Furthermore, 65.4% of the nurses reported a decrease in incidents related to the delivery and administration of injectable preparations. More than half of the nurses answered that the new system had made it easier for them to collect information on medicines and helped them provide better nursing services. When the nurses were asked to make a general assessment of the new system, 90% rated the system as "good." The results of this survey indicate that keeping the ward pharmacy open on holidays contributes to the promotion of the proper use of medicines, reduction of risks related to injections and improvement in the quality of medical care.

Many medical accidents concerning errors in the administration of injections have been reported in recent years but many of them could be prevented through the active involvement of pharmacists in this respect. At the Department of Pharmacy of the Municipal Ikeda Hospital, a ward pharmacy was established in April 2000 and the dispensing of injections, including the mixing of injections, was commenced. In October, 2001, an injection distribution surveillance system was also established. Under the system, injections are distributed to the patients' bedsides, information provided on the drugs in them and monitoring performed.We conducted a survey of the dispensing of injections and the surveillance system. The mixed injection preparations targeted by the survey were drip infusions for administration between 10 : 00 and 22 : 00 whose prescriptions were received by the Department of Pharmacy by 17 : 00 on the day before use, and injection preparations were mixed 4 times a day.The dispensing of injections was divided into 5 tasks : receipt of dispensing requests, preparation of labels, measuring of quantities, mixing of preparations, and preparation of infusion sets and each task was investigated for dispensing errors.Warnings were issued under the distribution surveillance system when pharmacists misidentified patients in distributing injections to the patient's bedside and the situation was investigated.The rate of pharmacist errors in mixing injection preparations was 2.23 % in a 4-month period and though 0.04% of the preparations in error were sent to wards, they were not administered to patients. Out of the 7, 690 instances in which injections were distributed to the patient's bedside by pharmacists in the 4-month period, in 3 instances (0.04%) pharmacists were warned about misidentifying patients. All of errors were human errors, but did not lead to errors in administration. This study suggests that risk of errors made with injections could be avoided by the close involvement of pharmacists in the work of administering injections. Greater use of codes was suggested for preventing human errors in future, since codes were printed on the injection in only 14.5 % of the injections distributed during our survey. Besides the increased use of such codes, the development of an injection dispensing surveillance system using them is also necessary.

Municipal Ikeda Hospital established a palliative care team consisting of physicians, pharmacists, and nurses in February 2002. We investigated the amounts of narcotics used during a period of 5 years, and evaluated the role of pharmacists in the palliative care team based on the trend in the amounts used. The total amounts of narcotics administered varied irregularly during the period but the use of rapid-release morphine hydrochloride products rapidly increased after fiscal 2002. On comparison of the numbers of administration days and the amounts of narcotics used between fiscal 1999 and 2003, the distributions were similar with no significant differences. The proportion of patients treated with rescue prescriptions, both internal and external use preparations, was about 10% until fiscal 2001, but this rapidly increased after fiscal 2002, and reached 71.4% in fiscal 2003. Rescue prescriptions are essential for setting dose escalation for narcotics and sudden appearance of severe pain, and thus the rescue prescription rate could be a means of evaluating the palliative care team. The rapid increase in the amount of rapid-release morphine hydrochloride products administered and the increase in the rescue prescription rate may have resulted from case study meetings, inauguration of cancer pain therapy programs, and subsequent instruction provided by pharmacists to the palliative care team.

At Ikeda Municipal Hospital, we created an order entry system for the dispensing and mixing of injections in November 2003. We then compared the numbers of injections that pharmacists mixed and administered to patients, the rates for injections mixed by pharmacists, return rates for injections mixed by pharmacists and dispensing error rates between the four months before and after introducing the system. Compared to before the introduction of the system, the number of injections that pharmacists mixed and administered to patients increased by about 40%, the rate for injections mixed by pharmacists increased by 2% and the return rate for injections decreased by approximately 1%. The dispensing error rate decreased to 0.26%, a marked drop from the 2.23% error rate before introducing the system. Based on these results, we felt that our order entry system for the dispensing and mixing of injections was very useful.

The system of intravenous injections (i.v.) being mixed by pharmacists is necessary to prevent contamination and dispensing errors. Such a system was started at the Municipal Ikeda Hospital on April 2000. The dispensing of injections consists of five steps, including the labeling, dispensing, setting and mixing, and the application of check systems. Dispensing errors that induced serious medical complications were examined over a 4-month period (2000.10. 1-2001. 1.31). In addition, resource management during dispensing errors were researched, and countermeasures against dispensing errors were developed. Dispensing errors involving i.v. mixing, which were identified after the preparation had been taken to the ward by nurses, were also surveyed for a 4-month period (2001. 6. 1-9.30). There were 9, 611 i.v. mixing by pharmacists in a 4-month period (2000.10. 1-2001. 1.31). There were 214 dispensing errors (2.23%) during those 4 months, those discovered in the final check comprised 0.28% (27cases), while those involving i.v. mixing taken to the ward by nurses was 0.04% (4 cases). The percentage of serious dispensing errors was 0.01 % (1 case). Fortunately, these mixed i.v. preparations were not administered to patients. In the second survey, there were 10, 478 i.v. mixings by pharmacists in a 4-month period (2001. 6. 1-9.30). There was only 1 case (0.01 %) of a dispensing error involving i.v. mixing identified after being taken to the ward by nurses. There were no cases involving serious dispensing errors. These erroneous instances of i.v. mixing were not administered to patients. When these two surveys are compared, no significant difference was observed, but the number of errors decreased after the establishment of countermeasures to reduce dispensing errors. As a result, it became clear that dispensing errors could occur at any step, but they were preventable by both making several checks and by developing countermeasures against dispensing errors at each step.

A system that included both images and voice using a personal computer was developed to provide pharmaceutical instructions for outpatients at the medication counter. A touch panel was adopted for easy use by a wide range of age groups. The system consisted of such items as the “usage of externally applied drug”, “information on disease”, “patient education” and comprised eight items over all. A survey of 105 patients was conducted and almost all patients (95%) understood the drug-related information provided. This system was found to be an effective method for providing patients with easily understood drug-related information and most patients actually enjoyed using this system which led to an improved dissemination of important medication related information.

To facilitate mutual understanding between doctors and nurses, prevent errors, and assure quality control in the mixing intravenous drip solutions at Ikeda Municipal Hospital, the Department of Pharmacy manages changes in the mixing of solutions and provides appropriate information for drug use. We mix solutions for intravenous injection under uniform standards and also set up a satellite pharmacy to perform these functions in April 2000. This satellite pharmacy accepts prescriptions for manual intravenous injections and manages two laminar air follow cabinets and a laminar flow biological safety cabinet. A ward trial was started in April, another ward was added in June and all wards were included in October 2000. We mix solutions for intravenous injection from Monday till Friday, based on prescriptions received the previous day, from four divisions. The hours of operation are from 10 : 00 Am to 8 : 00 Pm excluding weekends and holidays. The preparation of anticancer and narcotic drugs is not performed by the satellite pharmacy. We mixed 60 to 70 bottles of intravenous injections per day, over a six-month period. Of the intravenous injections mixed, about 70 percent were mixed by the Department of Pharmacy. 95.3 percent were used, 1.8 percent diverted, 2.9 percent were not used.

One of the side effects of cancer chemotherapy is the occurrence of stomatitis. Many studies have shown the effectiveness of a 0.1% allopurinol gargle for treating such stomatitis. Allopurinol gargle develops crystalline deposition a few days after preparation, and therefore it should befreshly prepared each time before use.We developed a prescription that delays crystalline deposition by adding glycerin to allopurinol gargle.Sterile allopurinol gargle (sterile ALT) was prepared by crushing allopurinol tablets, and then glycerin was added at various concentrations.The dissolved amount after 30 days was 0.65±0.05 mg/mL in sterile ALT without glycerin (sterile G0-ALT), 0.75±0.01 mg/mL in sterile ALT containing 1% glycerin (sterile G1-ALT), 0.79±0.03 mg/mL in sterile ALT containing 3% glycerin (sterile G 3-ALT), 0.89±0.06 mg/mL in sterile ALT containing 5% glycerin (sterile G 5-ALT), and 0.98±0.01 mg/mL in sterile ALT containing 10% glycerin (sterile G 10-ALT). The dissolved amount increased with the glycerin concentration.Allopurinol crystal deposition was observed after 2 days in sterile G 0-ALT, after 3 days in sterile G 1-ALT, after 6 days in sterile G 3-ALT, and after 10 days in sterile G 5-ALT, but could not be detected even after 30 days in sterile G 10-ALT.In tests of the sensation tastes during use in normal subjects, similar results were obtained between sterile G 10-ALT and sterile G 0-ALT. The xanthine oxidase (XOD) inhibitory activity was also similar between the two gargles.These results show that sterile G 10-ALT can be preserved for 30 days at 25°C, and its effects and sensation during use are similar to those of a prescription not containing glycerin.

Obesity contributes to the development of insulin resistance and the subsequent incidence of Type 2 Diabetes Mellitus (T2DM). The effects of co-administration of sitagliptin (dipeptidylpeptidase-4 inhibitor) and pitavastatin (lipid-lowering drug) on hyperinsulinemia and fatty liver damage accompanied by obesity in the preclinical stages of T2DM have not yet been investigated. We aimed to evaluate the additive effects of co-administration of sitagliptin and pitavastatin on hyperinsulinemia and fatty liver damage in obese ob/ob mice. Normal male C57BL/6J mice and obese ob/ob mice were divided into four groups, each receiving different drugs: standard mice chow, n = 8 (Normal); ob/ob mice with vehicle, n = 8 (Control); sitagliptin, n=8 (SG); pitavastatin+ sitagliptin, n = 8 (SG + PS). At the end of the study period (8 weeks), blood samples were drawn from all mice to determine Glycated Hemoglobin (HbA1c), serum glucose, insulin, triglyceride, total cholesterol, High-Density Lipoprotein (HDL) cholesterol, Aspartate-Aminotransferase (AST), Alanine Aminotransferase (ALT) and leptin levels. The SG+PS group had significantly (P < 0.05) lower levels of HbA1c, serum insulin, total cholesterol, AST, and ALT, and liver weight ratio, than did the Control group. And also, the SG+PS group had significantly (P < 0.05) higher levels of leptin than did the Control group. Body weight and serum glucose levels in the SG+PS group did not significantly decrease compared to those in the Control group. Serum triglyceride and HDL-cholesterol levels were unchanged among the four groups. These results suggest that combination treatment with sitagliptin plus pitavastatin may be a promising therapeutic approach in the management of T2DM because it has a beneficial effect on the pathophysiological processes of obesity.

The Chinese herbal medicine, Goshajinki-gan (GJ) (Niu-Che-Sen-Qi-Wan), has been widely used for treating patients with melalgia, lower back pain, numbness, and diabetic neuropathy. We investigated the effects of GJ on the regulation of serum insulin and triglyceride levels in obese Zucker fatty rats (fa/fa; ZFR). We administrated GJ to 6-week-old ZFR and non-obese lean rats (LR) for 12 weeks. Body weight and serum glucose, insulin, total cholesterol, and triglyceride levels were significantly increased at 18 weeks in ZFR as compared to the LR. GJ treatment in ZFR significantly suppressed elevation in serum glucose, insulin, and triglyceride levels, but no significant differences were observed in body weight and serum cholesterol levels in the ZFR group with GJ treatment compared to the ZFR group without GJ treatment. These results suggest that GJ may improve hyperinsulinemia and hypertriglyceridemia in ZFR and that GJ may be useful for preventing or delaying the onset of diabetes mellitus in a pre-diabetic state.

To prescribe drugs or check a prescription, it is very important to understand the contraindications. We developed an original drug information system utilizing commercialy available application software. On the base of this system, we made a list of drugs sequenced due to each contraindication and a list of drugs contraindicated due to drug interactions for combination use. Thus, this list enables us to save times in our searching for the information.