Effects of Capsaicin Coadministered with Eicosapentaenoic Acid on Obesity-Related Dysregulation in High-Fat-Fed Mice.

Obesity-induced inflammation contributes to the development of metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether the combination of eicosapentaenoic acid (EPA) and capsaicin could protect against high-fat diet (HFD)-induced obesity and related metabolic disorders. The experiments were performed using male C57BL/6J mice that were fed one of the following diets for 10 weeks: standard chow (5.3% fat content) (normal group), a HFD (32.0% fat content) (HFD group), or a HFD supplemented with either 4% (w/w) EPA (EPA group) or a combination of 4% (w/w) EPA and 0.01% (w/w) capsaicin (EPA+Cap group). Our results indicated that the body, fat and liver tissue weights and levels of serum glucose, insulin, total cholesterol, triglyceride, high-density lipoprotein-cholesterol, aspartate aminotransferase, and alanine aminotransferase were significantly higher in HFD group mice than in normal group mice (p<0.05 in all cases). However, the body and fat tissue weights and serum glucose levels and homeostasis model assessment of insulin resistance were significantly lower in EPA+Cap group mice group than in HFD and EPA group mice (p<0.05 in all cases). Thus, our study suggests that the combination of EPA and capsaicin might be beneficial for delaying the progression of obesity-related metabolic dysregulation and subsequent complications.

Effects of eicosapentaenoic acid on hepatic dyslipidemia and oxidative stress in high fat diet-induced steatosis.

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 < 0.01). In contrast, hepatic triglyceride and total cholesterol levels were significantly decreased in the HFD + EPA group, in comparison with those of the HFD group (p < 0.05). In addition, EPA decreased the body weight of obese mice and improved hepatic function. Hepatic superoxide dismutase activity and glutathione levels were significantly decreased in obese mice, but increased with EPA administration. Our data suggest that EPA supplementation has a beneficial effect on NAFLD progression.

[The Current State of Inappropriate Drug Use among Elderly Assisted-Living Residents].

Previous studies have reported that elderly assisted-living residents use multiple drug combinations and inappropriate drugs.The aim of this study was to assess the drug use and its consequences in residents of a nursing facility.We examined the prescriptions of all residents in a nursing facility in Osaka from their medical records.Of the total 67 residents, 48 were women.The average age of the residents was 86 years, the average number of prescription drugs they took was 6.4, and the average number of diseases present was 4.9. Correlation between the number of diseases and the drugs taken was significant (p<0.05), but the correlation between the degree of independence for activities of daily living and the number of the drugs taken was not significant.The most commonly present health condition was bone fracture.About 50% of the residents used a psychotropic drug and prescription drugs such as amantadine and hydroxyzine, which are not advisable for elderly people.It is necessary for the elderly to avoid the use of drugs that cause delirium and drowsiness, and future studies should focus on methods to prevent disuse syndrome in the elderly.

[Evaluation of the pharmaceutical stability of polaprezinc/sodium alginate gargle solution containing lidocaine].

OBJECTIVE: A gargle solution(L-P/AG)for the treatment of painful stomatitis was prepared by adding lidocaine to a polaprezinc/sodium alginate gargle solution(P/AG), and its pharmaceutical stability was evaluated. METHODS: L-P/AG was stored at 5, 25, and 40°C. The strengths of polaprezinc and lidocaine were determined. The viscosity and pH of L-P/AG were also determined, and its appearance was evaluated. RESULTS: When stored at 5 or 25°C in a dark place, L-P/AG showed neither reduction in the strength of either drug nor did it show a change in the viscosity, pH, or appearance. When stored exposed to light at 40°C, L-P/AG showed reductions in the strength of both drugs, as well as in viscosity and pH; furthermore, a change in appearance was noted. DISCUSSION: L-P/AG prepared for the treatment of painful stomatitis remains pharmaceutically stable for 28 days when stored at 25°C in a dark place.

[Thoughts and suggestions of pharmacists who participated in a home medical care training workshop in a local area].

We organized a home medical care training workshop to offer community pharmacists an opportunity to advance home medical care by allowing pharmacists in regional medicine to collaborate with local pharmacist groups. A questionnaire was administered to all participants after the workshop. On average, participants rated the overall quality of the workshop as 8.46 out of 10. Our results revealed that 72.5% of participating pharmacists were experienced in home medical care, with the majority having between 5 and 10 years of experience. Participants suggested that the qualities necessary for effective home medical care were knowledge of home-based care, positive attitude, and coordination with different home medical care staff members. Participants also made suggestions for lectures in future workshops (e.g., upskilling to improve home medical care expertise). In conclusion, participants in a home medical care training workshop primarily desired to learn skills for home medical care. To this end, consecutively holding the workshop and a cooperation support system with other medical and care professionals would be indispensable.

[Opinions of and conscious changes in pharmacists who participated in home medical care training workshop:].

We organized a home medical care training workshop to offer community pharmacists an opportunity to learn more about home medical care. The workshop consisted of lectures by the doctor, the nurse, and the pharmacist. A questionnaire was handed out to all the participants once the workshop had ended. On an average, the participants rated the overall quality of the workshop as 8.1 out of 10. Our results revealed that 62.7% of the participating pharmacists were experienced in home medical care, with the majority having between 1 and 5 years of experience. Most pharmacists with experience in home care had provided services such as delivering medicines to or instructing patients on the use of medicines at patient homes. Participants suggested that the qualities necessary for providing effective home medical care were knowledge of home-based care and a positive attitude, among others. Participants also made suggestions for lecture contents in future workshops, such as contract procedures or specific cases of home medical care. Furthermore, participants expressed many positive opinions such as the desire to hear the views of other professionals on home medical care. In conclusion, participation in the home medical care training workshop increased the participants' desire to learn and perform home medical care. This indicates that a subsequent workshop with the cooperation of other professionals is indispensable.

[Nutritional assessment employing the malnutrition universal screening tool for patients with colorectal cancer undergoing outpatient chemotherapy].

OBJECTIVE: We surveyed the nutritional status of patients with colorectal cancer undergoing outpatient chemotherapy using the malnutrition universal screening tool(MUST)to examine its usefulness and association with adverse events. METHODS: We examined the use of the MUST and the incidences of adverse events in 34 patients with advanced or recurrent colorectal cancer who had undergone outpatient chemotherapy between April and December 2010. RESULTS: The high-risk patients requiring nutritional care intervention comprised 47. 1%(16 patients)of the study population, and these patients exhibited significant decreases in body weight and body mass index. The incidences of appetite loss and fatigue were significantly higher in the high-risk group than in the low-risk group. DISCUSSION: Precautions against adverse events may prevent a worsening of the nutritional status of patients with colorectal cancer. Thus, nutritional assessment is necessary in patients undergoing outpatient chemotherapy. Furthermore, the MUST appears to represent a very useful simplified nutritional screening method for the nutritional management for these patients.

[A questionnaire survey for pharmacists participating in a home medical care training workshop].

To clarify the issues associated with promoting pharmacists' participation in home medical care(HMC), we performed a questionnaire survey for pharmacists who participated in a HMC training workshop. The cumulative number of participants in the workshop was 284; the majority of the participants was from mid-sized pharmacies and had been working for over 10 years. The rate of pharmacists engaged in HMC was 69% and their main practices were "drug delivery to patients" and "drug administration guidance for patients at home". Many participants responded that the key items for HMC were "cooperation with people with different type of jobs", "a wide pharmaceutical knowledge", and "effective involvement with patients and their families". The present main issues regarding HMC were "low pharmaceutical care fees", "deficiency of pharmacists", and "insufficient collaboration with people with different type of jobs". In order to resolve these issues, it is necessary to construct a cooperation system with other medical and welfare-related societies and to continuously organize such workshop.

Changes of intestinal mucosal and plasma PYY in a diarrhea model rat and influence of loperamide as the treatment agent for diarrhea.

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.

Changes of the peptide YY levels in the intestinal tissue of rats with experimental colitis following oral administration of mesalazine and prednisolone.

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.

Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells.

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<0.05). Further, at doses of 400 and 1000 microg/ml, Lf inhibited the enhancement of LPS-mediated permeability in Caco-2 cell monolayer. The results of this study suggest that Lf may have protective effects against LPS-mediated intestinal mucosal damage and impairment of barrier function in intestinal epithelial cells.

Assessment of palliative care team activities--survey of medications prescribed immediately before and at the beginning of opioid usage.

We established the Terminal Care Study Group, consisting of physicians, pharmacists, and nurses, in September 2001, and developed the group into the Palliative Care Team. We have surveyed the state of concomitant medications immediately before and at the beginning of opioid usage (except injections) to assess the role of the Palliative Care Team. The survey period was 3 years from October 1, 2002 to September 30, 2005. While the frequency of the prescription of non-steroidal anti-inflammatory drugs (NSAIDs), laxatives, or antiemetics before the beginning of opioid administration did not differ significantly among the 3 periods, that at the beginning of opioid administration increased significantly in 2003 compared with 2002, and increased further in 2004. Many of the drugs used were those that were recommended in our cancer pain management program. Thus, the activities of the Palliative Care Team are considered to have led to proper measures for the control of the major adverse effects of opioids such as constipation and nausea/vomiting in addition to pain control in accordance with the WHO's pain ladder, and also contributed to improvements of the patients' QOL.

Approach for differentiating trophoblast cell lineage from human induced pluripotent stem cells with retinoic acid in the absence of bone morphogenetic protein 4.

INTRODUCTION: Placental transport is the first step in chemotherapeutic safety evaluations during pregnancy. However, a well-established in vitro model is not available. We previously reported that a trophoblast layer model using differentiating choriocarcinoma JEG-3 cells (DJEGs) can be used for placental drug transport studies. However, it was necessary to increase the similarities between the syncytiotrophoblast, the main layer of the placental barrier, and the in vitro evaluation model in order for the model to be useful for placental drug transport evaluations. We focused on in vivo similarities of differentiating induced pluripotent stem cells (iPSCs). iPSCs can achieve a syncytiotrophoblast-like form and secrete human chorionic gonadotropin (hCG) following bone morphogenetic protein 4 (BMP4) treatment. However, BMP4-treated iPSCs can differentiate into several cell types. In the placental transport model, a dense syncytiotrophoblast cell layer is necessary for appropriate differentiation. METHODS: The conditions permitting differentiation of iPSCs into syncytiotrophoblasts with retinoic acid (RA) treatment without BMP4 were investigated. The presence of syncytiotrophoblast-like cells was confirmed by measurement of mRNA expression levels of breast cancer resistance protein (BCRP) and paternally expressed 10 (PEG10) in syncytiotrophoblasts. In addition, immunofluorescence imaging of cytokeratin 7 (CK7) induced in trophoblasts was performed. RESULTS: and Discussion: RA-induced iPSCs exhibited these syncytiotrophoblast-like features and hCG secretion was maintained for at least 28 days after treatment with RA (500 nM) without BMP4. These results suggest that RA-induced iPSCs are a suitable in vitro syncytiotrophoblast model that can be used as an indicator of drug placental transport for pharmacotherapy during pregnancy.

Effects of lipopolysaccharide on intestinal P-glycoprotein expression and activity.

It is well known that pharmacokinetics is often altered by changing the expression and activity of P-glycoprotein during sepsis. However, there have been few reports about expression and activity of P-glycoprotein in the small intestine during sepsis. We examined the levels of intestinal P-glycoprotein expression and activity using a rat sepsis model induced by lipopolysaccharide (LPS, from Escherichia coli). LPS was administered to male Wistar/ST rats intraperitonealy (i.p.) at 5 mg/kg. The small intestine was excised before and 1, 3 and 7 days after LPS administration, and the intestinal P-glycoprotein expression was determined using Western blot analysis. The activity of P-glycoprotein was evaluated by measuring the efflux of rhodamine-123 (Rho123) in rats using an in situ single perfusion method. The changes of permeability via the paracellular route were evaluated by measuring the amount of fluorescein isothicyanate-dextran 4400 (FD-4) in a similar way. On Day 1 after LPS administration, both the level of P-glycoprotein expression and the total amount of Rho123 excreted into the intestinal lumen decreased significantly, but levels of both AUC2-95 and CLtot were not significantly different as compared with the control group. On Day 3, the total P-glycoprotein, including intestinal P-glycoprotein, might have been induced by sepsis, and then the excretion of P-glycoprotein substrate drugs into the intestinal lumen increased more than that of the control group. On Day 7, all pharmacokinetic parameters returned to the control level. Thus the intestinal P-glycoprotein function recovered within 3 days of LPS administration.

[Proceedings of clinical pharmacy research with the cooperation of community and hospital pharmacist and pharmacy school].

The new pharmaceutical education system starts in Japan, those constructions are performed at a lot of universities aiming at the execution of a common examination and the clinical training, and the workshop for directive pharmacists have been held actively since last year. Moreover, various educational lectures, open lectures, and the training lectures for on-site pharmacist's upskilling are carried out. However, a technical training and the lecture for research approach that supports the pharmacist in a pharmaceutical clinical research are little at the chance to learn the research methods. Now, many joint researches with university initiative or a university is performed, and the institution of presentation inexperience at academic society also exists in terms of a regional element, a staff arrangement side, etc, and also when the continuation is difficult, it looks mostly. It is necessary that the teacher of pharmacy school almost arranged in the whole country support positively a clinical research by the nearby pharmacist, and also it seems that a clinical teacher's role is large in the cooperation of pharmacy school and the medical institution. Moreover, in order to elucidate the scientific basis (mechanism) of a problem suggestion in the clinical spot, basic research in a pharmacy school is also required. We always need to advance a pharmaceutical clinical research by considering the basic research by pharmacy school in medical institution, considering clinical research by medical institution in pharmacy school, while cooperating mutually. In this article, I show how to advance pharmaceutical clinical research.

Effects of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on intestinal function in streptozotocin-induced diabetic rats.

We examined the effects of Hachimi-jio-gan (HJ) on the small intestinal function in streptozotocin (STZ)-induced diabetic rats. The rats had free access to pellets containing 1% HJ extract powder for 4 weeks after STZ administration. The intestinal disaccharidase (sucrase and maltase) activity was elevated in STZ-treated rats compared with control rats, whereas it was significantly reduced by HJ administration. This suggested that HJ suppresses or delays monosaccharide production in the small intestinal epithelium. In addition, the intestinal mucosal weights and DNA contents that were significantly increased in the STZ-treated rats were restrained to the control level by HJ treatment. Simultaneously, we examined the changes in the plasma levels of glucagon-like peptide 2 (GLP-2), which is a trophic factor specific for the intestine. The plasma GLP-2 levels significantly increased in the STZ-treated rats, whereas HJ decreased the plasma GLP-2 levels. Thus intestinal mucosal weights and DNA contents correlated with plasma GLP-2 levels in diabetes-associated bowel growth. These results suggest that HJ may normalize or suppress the small intestinal disaccharidase activity and the epithelial cell proliferation mediated by GLP-2 in the animal model rats.

Enhanced Understanding of the Levels of Palliative Care in Pharmacy Students Through Participating in Clinical Training in Hospitals.

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.

Immunochemical characterization and measurement of neuronal type nitric oxide synthase in human neuroblastoma NB-OK-1 cell using novel anti-synthetic peptide antibody and specific immunoassay system.

We developed a sensitive and specific immunoassay system for human neuronal nitric oxide synthase (hnNOS) using synthetic hnNOS(998-1024) peptide and anti-hnNOS(998-1024) antibody. The novel antibody and radioimmunoassay system revealed a typical nNOS protein in human neuroblastoma NB-OK-1 cell (160 kDa, 180 fmol/10(6) cells). The kinetic parameters of the enzyme were K(m)=4.88 microM and V(max)=4.34 pmol/min/mg protein for L-arginine. On incubation of NB-OK-1 cell for 24 h, betamethasone phosphate decreased both nNOS-immunoreactivity (nNOS-IR) and enzymatic activity in the cell dose-dependently. On the other hand, pituitary adenylate cyclase activating polypeptide(1-38) (PACAP38) increased both nNOS-IR and enzymatic activity at concentrations of 10(-10) and 10(-9) M, but inversely decreased both at 10(-7) M. These suggest the positive and negative implications of endogenous NO in proliferation and differentiation of the cell, which support mitogenic activity of NO generated by nNOS in the cell. The present findings also provided evidence that the quantitative change of nNOS protein controls the integrated activity of the enzyme in the cell and, in turn, substantiate the validity and reliability of the present immunoassay system for hnNOS and its practical usefulness.

Protective effects of the herbal medicine goshajinkigan in a rat model of non-alcoholic fatty liver disease.

This study was designed to investigate the effect of an herbal medicine-goshajinkigan (GJ)-on the regulation of total body weight, as well as liver and adipose tissue weights in rats fed a highfat diet (HFD) and drinking of 30% sucrose (HFDS) (HFD; the rats received 19.6% energy from carbohydrates, 18.2% from proteins, and 62.2% from lipids; total energy, 506 kcal/100 g). Control rats were fed a standard diet (the rats received 60.5% energy from carbohydrates, 26.2% from proteins, and 13.3% from lipids; total energy, 360 kcal/100 g). Over a period of 12 weeks, rats were allowed free access to either the standard diet or HFDS containing 0, 1, or 3% GJ. In comparison with the control group, the HFDS rats showed a significant decrease in overall body weight and adipose tissue weight, and an increase in liver weight at 12 weeks. GJ treatment significantly reversed the HFDS-induced decrease in body and adipose tissue weight and reduced the elevated liver weight dose-dependently. Similarly, GJ reduced the elevated serum aspartate aminotransferase levels observed in HFDS rats. These results suggest that GJ may have the potential to alleviate damage to the liver in subjects with long-term consumption of HFDS.

In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells.

Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low-molecular-weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG-3 choriocarcinoma cells under different culture conditions and establishing the appropriate model of in vitro syncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG-3 cell layers. The mRNA expression levels of non-expressed in choriocarcinoma clone 1 (NECC1) and breast cancer resistance protein (BCRP), and those of E-cadherin (ECAD) and cadherin-11 (CDH11), which are adherens junction-associated proteins related to fusogenic ability of syncytiotrophoblasts differentiated from cytotrophoblasts, protein expression levels were considered as the differentiation signals. The highest TEER values were obtained in the JEG-3 cells cultured in the Dulbecco's modified Eagle's medium (DMEM)/Ham's F-12 (1:1) mixed medium (CS-C(®) ; Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan). By comparing the TEER values and the differentiation signals, the authors identified at least five JEG-3 cell-differentiation patterns. The differentiation pattern of JEG-3 cultured in CS-C resembled the syncytiotrophoblast-like differentiation signal characterizations in vivo. In conclusion, the syncytiotrophoblast-like models of differentiating JEG-3 cells cultured in CS-C might be appropriate for evaluating drug transport across the placental trophoblast.