Changes in Pharmacy Students' Awareness of Hepatitis B Patients through Patient Lectures as Humanity Education: Findings from Questionnaire Surveys of Face-to-Face and Simultaneous Remote Classes.

In 2020, the coronavirus disease 2019 (COVID-19) pandemic made social distancing compulsory. In patient lectures by hepatitis B patients (Patient Lectures)-a humanity education initiative that had traditionally been delivered face-to-face to assembled students-it was necessary to divide the students into two groups, one that attended the Patient Lectures in person (face-to-face group) and another that assembled in a separate room to view the delivered lecture simultaneously and remotely via a teleconferencing platform (remote group). To investigate possible changes in students' awareness of hepatitis B patients before (pre-) and after (post-) the lecture that year, the face-to-face and remote-attendance groups were analyzed separately. The participants were 203 fourth-year students belonging to the Faculty of Pharmaceutical Sciences at Japan's Setsunan University, whose pre-clinical education curriculum prior to pharmacy practice experience included a Patient Lecture. The students were divided into two groups based on their student-ID numbers. Survey questionnaires were completed anonymously before and after the Patient Lecture. The students' awareness of hepatitis B patients' experience changed significantly after attending the Patient Lectures; this change was similar in both the face-to-face and remote-attendance groups. Regarding the possibility of hepatitis B virus infection, the remote group selected fewer answers implying strong convictions than did the face-to-face group, and both groups perceived several issues incorrectly. Although slight differences were observed between the two groups, the changes before and after the lectures were similar, indicating that humanity-education lectures are worthwhile not only when delivered in face-to-face contexts but also when delivered and viewed remotely within a class setting.

Therapeutic Strategy for Rheumatoid Arthritis by Induction of Myeloid-Derived Suppressor Cells with High Suppressive Potential.

Combination treatment using fingolimod (FTY720), an immunomodulator, and a pathogenic antigen prevents the progression of glucose-6-phosphate isomerase (GPI)325-339-induced arthritis. In this study, we focused on myeloid-derived suppressor cells (MDSCs; CD11b+Gr-1+ cells) and investigated the effects of the combination treatment on these cells. DBA/1J mice with GPI325-339-induced arthritis were treated using FTY720 and/or GPI325-339 for five days. The expanded CD11b+Gr-1+ cell population and its inhibitory potential were examined. The percentage of CD369+CD11b+Gr-1+ cells effectively increased in the combination-treated mice. The inhibitory potential of CD369+CD11b+Gr-1+ cells was higher than that of cells not expressing CD369. Among bone marrow cells, the expression of CD369 in CD11b+Gr-1+ cells increased following stimulation with granulocyte-macrophage colony-stimulating factor, and the expression of CD11c increased accordingly. The increased CD11c expression indicated a decrease in the potential to suppress T cell proliferation based on the results of the suppression assay. The percentage of CD11c-CD369+ cells in CD11b+Gr-1+ cells that were induced by the combination treatment also increased, and these cells tended to have a higher capacity to inhibit T cell proliferation. In conclusion, the combination treatment using FTY720 and the pathogenic antigen effectively induces MDSC, which demonstrates a high potential for suppressing T cell proliferation in the lymph nodes, thereby establishing an immune-tolerant state.

Sivelestat's effect on Candida albicans water-soluble fraction-induced vasculitis.

BACKGROUND: We investigated the efficacy of sivelestat sodium hydrate (SSH) as a treatment for Kawasaki disease, and its pharmacological action sites, in mice with Candida albicans water-soluble fraction-induced vasculitis. METHODS: Sivelestat sodium hydrate was administered intraperitoneally to Candida albicans water-soluble fraction-induced vasculitis model mice to assess its efficacy in preventing the development of coronary artery lesions based on the degree of inflammatory cell infiltration in the aortic root and coronary arteries (vasculitis score). The pharmacological sites of action were investigated based on changes in neutrophil elastase (NE) and intercellular adhesion molecule 1 (ICAM-1) positive areas, ICAM-1 and tumor necrosis factor-α mRNA expression levels in the upper heart, and the proportion of monocytes in the peripheral blood. RESULTS: The vasculitis score decreased below the lower limit of the 95% confidence interval of untreated mice in 69% of the SSH-treated mice. The NE- and ICAM-1-positive regions, and the mRNA expression of ICAM-1 and tumor necrosis factor-α were lower in the SSH-treated mice than in the untreated mice. The proportion of monocytes in the peripheral blood was higher in the SSH-treated mice than in the untreated mice, whereas monocyte migration to inflammation areas was suppressed in the SSH-treated mice. CONCLUSIONS: Our results showed that SSH might prevent the development of coronary artery lesions and ameliorate disease activity. In addition to its NE-inhibitory effect, SSH sites of action may also include monocytes.

Preventive effect of edaravone ointment on cyclophosphamide-chemotherapy induced alopecia.

PURPOSE: We evaluated the preventive effect of the antioxidant edaravone (EDR) on chemotherapy-induced alopecia (CIA) to improve quality of life in cancer patients. METHODS: Hair loss was induced by intraperitoneally administering cyclophosphamide (CPA, 75 mg/kg) to rats, and topically applying EDR ointment (100 mg/day) once daily for 16 days (when hair loss starts) or 21 days (just before hair growth). The rats were divided into four groups: control group (without CPA or EDR), EDR 0% group (CPA + EDR 0%), EDR 3% group (CPA + EDR 3%), and EDR 30% group (CPA + EDR 30%). The prevention of CIA was evaluated by the hair coverage score (five levels from 0 to 4). Furthermore, we measured the size of the hair follicle area and the expression levels of insulin-like growth factor (IGF)-1 mRNA in dermal papilla cells. RESULTS: The EDR 3% and EDR 30% groups exhibited higher hair coverage scores than the EDR 0% group on day 16 and day 21. On day 16, the hair follicle area in the EDR 3% and EDR 30% groups was significantly larger than that in the EDR 0% group. Furthermore, IGF-1 expression levels in the EDR 3% group were significantly higher than those in the EDR 0% group. On day 21, no significant difference was observed in hair follicle area or IGF-1 mRNA levels among the groups. CONCLUSION: Our results show that EDR administration lessened hair loss due to CPA in a dose-independent manner above doses of 3%, suggesting potential applications beside chemotherapy.

Characterization of an Expanded IL-10-Producing-Suppressive T Cell Population Associated with Immune Tolerance.

An increase in the number of glucocorticoid-induced tumor necrosis factor receptor-family related gene/protein (GITR)+CD25- (or fork-head box protein 3: Foxp3-) CD4+ T cells, after treating a mouse model of arthritis with fingolimod (FTY720), and a pathogenic antigen may play a key role in the establishment of immune tolerance. In this study, we characterized a specific expanded T cell subset in this population. Mice with glucose-6-phosphate isomerase peptide (GPI325-339)-induced arthritis were treated with FTY720 (1 mg/kg, per os) and GPI325-339 (10 µg/mouse, intravenously) for five days, starting from the onset of symptoms. The expanded GITR+CD25- (or Foxp3-) CD4+ T cell population and its cytokine production were examined using flow cytometry. Furthermore, time-dependent changes in T-bet and/or early growth response gene 2 (Egr-2) expression in this T cell subset were examined. The density of T cell immunoreceptors with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif domains (TIGIT)+CD39+ cell subset in the GITR+Foxp3-CD4+ T cell population was significantly increased only in the combined treatment group, compared to that in the untreated and single-treatment groups. In the TIGIT+CD39+GITR+Foxp3-CD4+ T cell population, T-bet+Egr-2+/T-bet+Egr-2- cell ratio increased in the latter stage of the treatment. Furthermore, this T cell subset, which corresponded to a T helper 1 (Th1) response, produced high levels of both interleukin (IL)-10 and interferon (IFN)-γ. In conclusion, expanded TIGIT+CD39+GITR+Foxp3-CD4+ T cells shifted from an effector Th1 to IL-10-producing-suppressor T cell phenotype, which may promote an immune-tolerant state.

Telmisartan Exacerbates Cisplatin-Induced Nephrotoxicity in a Mouse Model.

Cisplatin (CDDP; cis-diamine dichloroplatinum)-induced nephrotoxicity is the main reason for dose limitations, which can reduce the efficacy of cancer treatment. Lower blood pressure and administration of renin angiotensin system (RAS) inhibitors have been reported as factors that exacerbate CDDP-induced nephrotoxicity; however, the detailed mechanisms remain unknown and the results of previous studies are conflicting. In this study, we examined the influence of various hypotensive drugs, including RAS inhibitors and calcium channel blockers, on CDDP-induced nephrotoxicity in BALB/c mice. The mice were divided into nine groups: (1) CDDP group (15 mg/kg CDDP), (2) AML group (5 mg/kg amlodipine), (3) ENA group (2.5 mg/kg enalapril), (4) telmisartan (TEL) group (10 mg/kg telmisartan), (5) LOS group (10 mg/kg losartan), (6) CDDP + AML group, (7) CDDP + ENA group, (8) CDDP + TEL group, and (9) CDDP + LOS group. Nephrotoxicity was evaluated by measuring serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, the kidney sections were stained with Masson's trichrome and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) to assess the renal fibrosis area and apoptotic area. Serum CRE and BUN levels were increased in the CDDP + ENA, CDDP + LOS, and CDDP + TEL groups compared to those in the CDDP alone group, and the CDDP + AML group showed an increasing trend. However, there was no correlation between ∆CRE or ∆BUN levels and ∆ systolic blood pressure. The CDDP + TEL group showed a significant increase in the renal fibrosis area. These results suggest that exacerbation of CDDP-induced nephrotoxicity is not correlated with systolic blood pressure but is associated with administration of RAS inhibitors, particularly TEL.

Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice.

BACKGROUND: The increasing incidence and prevalence of atopic dermatitis (AD) demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of immunomodulator FTY720 ointment (fingolimod) for mite-induced intractable AD using an NC/Nga mouse model. METHODS: Female NC/Nga mice that developed severe AD were divided into four groups: (1) FTY720 (0.001% FTY720 ointment), (2) tacrolimus (tacrolimus hydrate ointment) (3) betamethasone (betamethasone ointment), and (4) ointment base (hydrophilic petrolatum), all of which received treatment six times per week. Therapeutic efficacy after two weeks was evaluated in terms of AD severity, histochemical observations (epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration), transepidermal water loss (TEWL), and epidermal barrier function (filaggrin expression). RESULTS: Betamethasone treatment showed little effect, confirming that the AD was intractable. In the FTY720 group, AD improved significantly compared with the ointment base group, as did epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration. In contrast, AD in the tacrolimus and betamethasone groups did not improve significantly, nor did epidermal hypertrophy or mast cell accumulation. Furthermore, in the FTY720 group, TEWL decreased significantly compared with the ointment base group, and filaggrin expression significantly increased compared with the betamethasone and ointment base groups. CONCLUSIONS: FTY720 ointment is a promising candidate for treatment of intractable AD. These findings also provide the first evidence that FTY720 ointment ameliorates epidermal barrier function.

Functional Mechanism(s) of the Inhibition of Disease Progression by Combination Treatment with Fingolimod Plus Pathogenic Antigen in a Glucose-6-phosphate Isomerase Peptide-Induced Arthritis Mouse Model.

We previously reported that combination treatment with fingolimod (FTY720) plus antigenic peptide of glucose-6-phosphate isomerase (residues 325-339) (GPI325-339) from the onset of symptoms significantly inhibited disease progression in a mouse model of GPI325-339-induced arthritis. In this study, we investigated the mechanism(s) involved. The model mice were treated from arthritis onset with FTY720 alone, GPI325-339 alone, or the combination of FTY720 plus GPI325-339. At the end of treatment, inguinal lymph nodes (LNs) were excised and examined histologically and in flow cytometry. Levels of apoptotic cells, programmed death-1-expressing CD4(+)forkhead box P3(-) nonregulatory T cells (non-Tregs), and cytotoxic T-lymphocyte antigen 4-expressing non-Tregs in inguinal LNs were markedly increased in the combination treatment group mice. Regulatory T cells (Tregs) were also increased. These results indicate that combination treatment with FTY720 plus GPI325-339 inhibits the progression of arthritis by inducing clonal deletion and anergy of pathogenic T cells and also by immune suppression via Tregs.

Preventive effect of free radical scavenger edaravone lotion on cyclophosphamide chemotherapy-induced alopecia.

PURPOSE: We investigated the inhibitory effect of edaravone (EDR) lotion on chemotherapy-induced alopecia (CIA) to improve the quality of life for patients with cancer. METHODS: Wistar rats were intraperitoneally injected with cyclophosphamide (CPA, 75 mg/kg) to induce CIA and divided into six groups: (1) Control; (2) EDR 0%; (3) EDR 0.3%; (4) EDR 3%. The TUNEL-positive area was examined histologically, and mRNA expression levels of the apoptosis-related factors, such as B-cell/CLL lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax), were determined. RESULTS: In the three CPA-treated groups, a decrease in the coverage score (percentage of hairs covered) was observed from days 16 to 18. In addition, coverage scores on day 21, the last day of observation, showed a tendency for the suppression of hair loss to increase, though hair loss was observed in all groups. The coverage scores of the EDR 0.3% and 3% groups after day 17 were significantly higher than those of the EDR 0% group. The TUNEL-positive area of skin tissue on day 16 was extensive in the EDR 0% group and decreased in the EDR 0.3% and 3% groups. The mRNA expression ratio of Bcl-2/Bax on day 21 was maintained at the same level as that of the control group only in the EDR 3% group. CONCLUSION: This study confirmed the use of EDR lotion to inhibit hair loss, indicating that the clinical application of EDR lotion may improve the quality of life for patients with cancer and their willingness to undergo treatment.

Efficacy of combination treatment with fingolimod (FTY720) plus pathogenic autoantigen in a glucose-6-phosphate isomerase peptide (GPI325-339)-induced arthritis mouse model.

Fingolimod (FTY720) is known to have a significant therapeutic effect in various autoimmune disease models. Here, we examined FTY720 in a model of rheumatoid arthritis, induced by immunizing DBA/1 mice with a peptide consisting of residues 325 through 339 of glucose-6-phosphate isomerase (GPI325-339). The efficacy was evaluated in terms of macroscopic findings, inflammatory cell infiltration and autoantibody level. Prophylactic administration of FTY720 from the day of immunization significantly suppressed the development of paw swelling, but therapeutic administration of FTY720 from onset of symptoms on day 8-9 was less effective. Interestingly, however, combination treatment with FTY720 plus GPI325-339 for 5 d after onset of symptoms significantly reduced the severity of symptoms in all mice, and no relapse occurred after booster immunization. Taking into account the reported mechanism of action of FTY720, these results indicate that combination treatment with FTY720 plus pathogenic autoantigen might efficiently induce immune tolerance by sequestering circulating autoantigen-specific lymphocytes from blood and peripheral tissues to the secondary lymphoid tissues. Combination treatment with FTY720 plus pathogenic autoantigen may become a breakthrough treatment for remission-induction in patients with autoimmune diseases including rheumatoid arthritis.

Therapeutic approach to steroid-resistant dermatitis using novel immunomodulator FTY720 (Fingolimod) in combination with betamethasone ointment in NC/Nga mice.

The therapeutic efficacy of the novel immunomodulator FTY720 (Fingolimod), alone and in combination with betamethasone ointment, was examined in the NC/Nga mouse model of spontaneous steroid-resistant dermatitis. Male NC/Nga mice which had developed severe dermatitis were divided into six groups: 1) a biweekly betamethasone group (betamethasone ointment, twice a week), 2) a daily betamethasone group (betamethasone ointment, six times a week), 3) an FTY720 group (FTY720, orally, three times a week), 4) a biweekly combination group (oral FTY720 plus betamethasone ointment, twice a week), 5) a daily combination group (oral FTY720 plus betamethasone ointment, six times a week) and 6) a placebo group (vehicle alone). The therapeutic efficacy was evaluated in terms of severity of dermatitis, epidermal hypertrophy, accumulation and degranulation of mast cells and infiltrated CD3+ T cells into the dermis after 4 weeks of treatment. Biweekly and daily betamethasone treatments had little effect, confirming that the dermatitis was steroid-resistant. In the FTY720 and biweekly combination groups, the dermatitis showed no marked improvement. In the daily combination group, the dermatitis was significantly (p<0.05, Mann-Whitney U-test) improved as compared with the FTY720 group, biweekly and daily betamethasone groups and placebo group. Further, epidermal hypertrophy and accumulation of mast cells were suppressed. Therefore, combination therapy with FTY720 and daily betamethasone ointment is a promising candidate for treatment of steroid-resistant atopic dermatitis.

[Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 (fingolimod) in combination with betamethasone ointment in NC/Nga mice].

BACKGROUND: The increasing incidence and prevalence of atopic dermatitis (AD) have led to a requirement for new means to treat the disease. We investigated the therapeutic efficacy of the novel immunomodulator FTY720 (Fingolimod), alone and in combination with betamethasone valerate ointment, in the NC/Nga mouse model of mite-induced intractable dermatitis. METHODS: Female NC/Nga mice in which dermatitis had been induced with Dermatophagoides farinae were divided into six groups: 1) a betamethasone group (betamethasone ointment, six times a week), 2) an FTY720 group (FTY720, orally, three times a week), 3) an FTY720 plus betamethasone ointment group, 4) an ointment base group (ointment base, six times a week), 5) an FTY720 plus ointment base group and 6) a placebo group (vehicle alone). The therapeutic efficacy was evaluated in terms of the severity of dermatitis and histochemical observations after two weeks of treatment. RESULTS: Betamethasone treatment had little effect, confirming that the dermatitis was intractable. In the FTY720 plus betamethasone ointment group, the dermatitis was significantly improved as compared with the betamethasone ointment and placebo groups. This combination therapy also suppressed epidermal hypertrophy and accumulation of mast cells and CD3+T-cells in dermis, all of which were observed in mice in which the dermatitis had become established. CONCLUSION: Our results strongly suggest that the combination of FTY720 plus betamethasone ointment is a promising candidate for treatment of intractable human AD.

Renin-angiotensin system inhibitors combined with cisplatin exacerbate cisplatin-induced nephrotoxicity in mice.

INTRODUCTION: We previously reported that the concomitant use of enalapril and telmisartan exacerbates the risk of cisplatin (CDDP)-induced acute renal dysfunction compared to other antihypertensive drugs in mice. Thus, in the current study, we investigated the risk of developing chronic kidney disease following repeated concomitant use of CDDP and antihypertensive drugs. MATERIALS AND METHODS: Male BALB/c mice were divided into 12 groups: (1) Control group (untreated), (2) CDDP group (7 mg/kg, CDDP), (3) AML group (5 mg/kg, amlodipine), (4) ENA group (2.5 mg/kg, enalapril), (5) TEL group (10 mg/kg, telmisartan), (6) LOS group (10 mg/kg, losartan), (7) CDDP+AML group (5 mg/mL, AML), (8) CDDP+ENA group (2.5 mg/kg, ENA), (9) CDDP+LowENA group (1.25 mg/kg, ENA), (10) CDDP+TEL group (10 mg/kg, TEL), (11) CDDP+LowTEL group (5 mg/kg, TEL), and (12) CDDP+LOS group (10 mg/kg, LOS). CDDP was administered intraperitoneally four times every 7 days, and each antihypertensive drug was administered orally from day 3 before CDDP administration until day 24 (six times a week). The degree of renal damage was assessed. The nephrotoxicity of each individual was evaluated by measuring serum creatinine and blood urea nitrogen levels. The degrees of renal fibrosis and epithelial-mesenchymal transition were also examined in kidney tissue sections. RESULTS AND DISCUSSION: The results suggest that combinatorial treatment of CDDP and renin-angiotensin system inhibitors, particularly ENA and TEL, may exacerbate CDDP-induced nephrotoxicity. This study clearly demonstrates the need for large-scale clinical studies to construct treatment regimens that do not interfere with the therapeutic intensity of CDDP.

Relapse of experimental autoimmune encephalomyelitis after discontinuation of FTY720 (Fingolimod) treatment, but not after combination of FTY720 and pathogenic autoantigen.

FTY720 (Fingolimod) is known to have a significant therapeutic effect on experimental autoimmune encephalomyelitis (EAE). Here, we used an EAE mouse model, which had been established by immunizing C57BL/6J mice with a partial peptide of myelin oligodendrocyte glycoprotein (MOG35₋55), to examine the relapse of EAE upon discontinuation of treatment with FTY720 alone or in combination with MOG35₋55. Relapse was confirmed to occur in all animals (n=6) within one week after discontinuation of FTY720, with increase in the number of lymphocytes infiltrating the spinal cord and demyelination. However, in the case of combination therapy with FTY720 and MOG35₋55, relapse following discontinuation of treatment was completely suppressed. The autoantigenic peptide might serve to suppress the clonal selection of relapse-associated autoantigen-specific T cells.

[Learning Strategy for Pharmacy Students to Develop Empathy for Hepatitis B Patients through a Lecture Presented by Patients Describing Their Daily Lives].

In April 2018, as part of their fifth-year pre-clinical education curriculum, pharmacy students at Setsunan University attended a lecture presented by hepatitis B patients and their lawyer entitled "Lecture by Hepatitis B Patients". This lecture was intended to help the students to understand the circumstances and difficulties encountered by hepatitis B patients on a daily basis. For this study, we conducted questionnaire surveys of the pharmacy students before and after the lecture. The survey items pertained to students' knowledge about hepatitis B (e.g., its spread and infection possibility in daily life). Students' responses before and after the lecture varied depending on the survey topic. Hepatitis B knowledge acquired by the students in their junior year increased after the lecture; moreover, attitudes to hepatitis B patients and understanding of the difficulties and prejudice that they experienced showed a significant change. For example, responses to the items, "Feel sympathy for patients suffering from discrimination and prejudice" and "Hard to work…" were much more sympathetic after the lecture; additionally, students were less likely to "Fear infection when near patients" and more likely "… to associate with patients". Thus, the "Lecture by Hepatitis B Patients" had a significant impact on the pharmacy students' perceptions of these patients, allowing them to cultivate greater empathy. From an educational standpoint, it is of the utmost importance for pharmacy/medical students to develop their humanity as members of healthcare teams. Educational real-world experiences, such as the "Lecture by Hepatitis B Patients", provide opportunities for this development.

Intravenous lipid emulsion therapy for acute clomipramine intoxication in rats.

AIM: In this study, to assess the utility of lipid emulsion (ILE) therapy as a treatment option for overdoses of lipophilic drugs, we examined the detoxification effect of ILE therapy in rats that were administered overdoses of the tricyclic antidepressant clomipramine hydrochloride (CMI). METHODS: Female Wistar rats were orally administered 50 mg/kg CMI five times in 2-h intervals to examine whether intralipos accelerated the elimination of CMI in the peripheral blood. Rats were divided into the intralipos (i.v. 2 g/kg intralipos) and placebo (i.v. saline) groups. The concentrations of CMI and desmethylclomipramine (DMCMI), a metabolite of CMI, in blood were measured over time by high-performance liquid chromatography. We then gave the animals 100 mg/kg CMI orally to examine whether intralipos could inhibit the distribution of CMI. The CMI and DMCMI concentrations in peripheral blood, liver, and brain were measured 60 min after intralipos administration. RESULTS: The blood concentration of CMI was significantly higher in the intralipos group than in the placebo group at 60 and 120 min. After a single administration of 100 mg/kg CMI, the ratio of the concentration of CMI in liver/serum was significantly lower in the intralipos group than in the placebo group. We also found a significantly faster elimination rate for CMI in peripheral blood in the intralipos group than in the placebo group. CONCLUSION: The distribution of CMI from blood to tissue was suppressed by intralipos. Therefore, ILE therapy is a promising candidate for the treatment of overdoses of lipophilic drugs.

Consideration of Preventing Local Venous Pain by Dacarbazine.

Local venous pain caused by dacarbazine (DTIC) injection is due to its photodegradation product 5-diazoimidazole-4-carboxamide (Diazo-IC). The production of Diazo-IC can be decreased by protecting the drug from light. Furthermore, the production of Diazo-IC reportedly increases with time; however, there are no studies reporting the association between the injection preparation time and local venous pain caused by the DTIC injection. We evaluated the efficacy of the following: (1) method used to shorten the injection preparation time and (2) method used to change the diluting solution for DTIC. We found that shortening the injection preparation time tended to decrease the local venous pain expression due to DTIC, and Veen F decreased the production of Diazo-IC compared with the normal saline and 5% glucose solution. These results indicate that shortening the injection preparation time may be effective in preventing the local venous pain caused by the DTIC injection; moreover, using Veen F for DTIC may also reduce the pain.

Combination treatment with fingolimod and a pathogenic antigen prevents relapse of glucose-6-phosphate isomerase peptide-induced arthritis.

INTRODUCTION: Combination treatment with fingolimod (FTY720) plus pathogenic antigen is thought to prevent glucose-6-phosphate isomerase (GPI)325-339-induced arthritis progression by effective induction of immune tolerance. Here, we examined the efficacy of this combination treatment on remission maintenance. METHODS: GPI325-339-induced arthritis mice were treated for 5 days with FTY720 (1.0 mg/kg, p.o.) alone, GPI325-339 (10 µg/mouse, i.v.) alone, or with the FTY720 plus GPI325-339 combination. In some experiments, mice were resensitized with GPI325-339. RESULTS: Following resensitization with GPI325-339, combination-treated mice exhibited neither severe relapse nor elevated lymphocyte infiltration in joints. Neither anti-human nor mouse GPI325-339 antibody levels were correlated with clinical symptoms. This suggests that combination treatment prevents relapse following resensitization via regulation of pathogenic antigen-specific T cells. The proportion of regulatory T (Treg) cells in inguinal lymph nodes was increased post treatment in the FTY720 alone and FTY720 plus GPI325-339 groups. In contrast, the proportion of glucocorticoid-induced tumor necrosis factor receptor-family-related gene/protein (GITR)(+) non-Treg cells was increased only in combination-treated mice. Furthermore, GITR(+) non-Treg cells, which were induced by the combination treatment in vivo, possess suppressive activity and high ability to produce interleukin (IL)-10. CONCLUSION: GITR(+) non-Treg cells might play a key role in relapse prevention following resensitization. Thus, this combination treatment might establish immune tolerance by induction of GITR(+) non-Treg cells.

[Concept extraction of graduate research by modified grounded theory approach and creating of rubric oriented to performance evaluation].

  A revised core curriculum model for pharmaceutical education, developed on the basis of the principles of outcome-based education, will be introduced in 2015. Inevitably, appropriate assessments of students' academic achievements will be required. Although evaluations of the cognitive domain can be carried out by paper tests, evaluation methods for the attitude domain and problem-solving abilities need to be established. From the viewpoint of quality assurance for graduates, pharmaceutical education reforms have become vital to evaluation as well as learning strategies. To evaluate student academic achievements on problem-solving abilities, authentic assessment is required. Authentic assessment is the evaluation that mimics the context tried in work and life. Specifically, direct evaluation of performances, demonstration or the learners' own work with integrated variety knowledge and skills, is required. To clarify the process of graduate research, we obtained qualitative data through focus group interviews with six teachers and analyzed the data using the modified grounded theory approach. Based on the results, we clarify the performance students should show in graduate research and create a rubric for evaluation of performance in graduate research.

[Studies Using Text Mining on the Differences in Learning Effects between the KJ and World Café Method as Learning Strategies].

The KJ method (named for developer Jiro Kawakita; also known as affinity diagramming) is widely used in participatory learning as a means to collect and organize information. In addition, the World Café (WC) has recently become popular. However, differences in the information obtained using each method have not been studied comprehensively. To determine the appropriate information selection criteria, we analyzed differences in the information generated by the WC and KJ methods. Two groups engaged in sessions to collect and organize information using either the WC or KJ method and small group discussions were held to create "proposals to improve first-year education". Both groups answered two pre- and post- session questionnaires that asked for free descriptions. Key words were extracted from the results of the two questionnaires and categorized using text mining. In the responses to questionnaire 1, which was directly related to the session theme, a significant increase in the number of key words was observed in the WC group (p=0.0050, Fisher's exact test). However, there was no significant increase in the number of key words in the responses to questionnaire 2, which was not directly related to the session theme (p=0.8347, Fisher's exact test). In the KJ method, participants extracted the most notable issues and progressed to a detailed discussion, whereas in the WC method, various information and problems were spread among the participants. The choice between the WC and KJ method should be made to reflect the educational objective and desired direction of discussion.