[Fostering Pharmacists to Succeed in a Drastically Changing Society].

In 2006, Japan's pharmaceutical science education was revised to a 6-year enrollment course, placing greater emphasis on cultivating practical clinical ability. Quality Assurance (QA) measures have been implemented including offering education based on a model core curriculum and third-party assessments. In August 2021, Ministry of Education, Culture, Sports, Science and Technology (MEXT) launched an investigative commission to review the above. For QA, the commission summarized a comprehensive report in August 2022 for items including: modality of selecting entrants; revising enrollment limits; securing education management; information disclosure; corresponding to pharmaceutical education assessments. For revising the model core curriculum, the commission is reviewing correspondence to: demographic changes due to decreasing birthrates, an ageing population, changes in the structure of diseases; rising and emerging infectious diseases; utilizing Big Data and artificial intelligence (AI). As Japan's ageing population is forecast to peak in 2040s, pharmacists must be fostered to provide safe and quality medicine towards a drastically changing future. Medical care is provided through the collaboration of various professions. In such changing demographics, team medicine is crucial to provide quality medical care. Moreover, towards all medical professions sharing the same vision, revisions to the model core curricula for medical and dental education are also being reviewed. The commission is now reviewing detailed curricula to foster pharmacists with competencies to: comprehensively assess patients and ordinary citizens; utilize information science and technology; professionalism. Towards securing quality pharmaceutical education, pharmaceutical departments at universities must also organize and implement an educational curriculum based on the Model Core Curriculum for Pharmaceutical Education. This paper will introduce the investigative commission's review.

[Report on a Psychiatric Clinical Practicum in Which Pharmacy Students Perform a Pharmaceutical Intervention].

Neuropsychiatric disorders are among the most represented disorders in the 2013 revision of the Model Core Curriculum for Pharmaceutical Education in Japan. However, it is reported that many pharmacy students have a negative impression of neuropsychiatric disorders because they do not know how to interact with psychiatric patients. To deepen students' understanding of pharmacotherapy for psychiatric disorders, Chiba University Hospital provides a one-day psychiatric clinical practicum in which pharmacy students perform a pharmaceutical intervention. In this practicum, students first had a group discussion about the case, assessed the pharmaceutical problem, and considered pharmacotherapy solutions to the problem on their own. Then, the students interviewed the patients directly to collect pharmaceutical-related information. Finally, the students participated in a conference and presented their own pharmacotherapy solutions to the problem. In this study, we conducted a questionnaire survey and assessed the students' reports in order to investigate their satisfaction with the practicum, changes in their impression of psychiatric disorders or patients with psychiatric disorders, and the level of knowledge they attained. The results showed that almost all students were satisfied with the practicum. The students' impression of psychiatric disorders or patients with psychiatric disorders changed in a positive direction. It seems that students came to realize the role and responsibility of the pharmacist in medical teams. These findings suggest that the practicum led to a positive change in the students' impression of psychiatric patients through conversations with the patients, assessment of pharmacotherapy from a pharmaceutical point of view, and proposing prescriptions.

[Questionnaire Survey of Pharmacy Students regarding Long-term In-hospital Practical Training: 8 Years of Changes].

In 2010, the in-hospital practical training period for pharmacy students was extended from 4 to 11 weeks. We have conducted questionnaire surveys of these students every year with the aim of reviewing the quality of training by conduction of surveys and evaluations. However, it was not clear whether reviewing based on the questionnaire results improved student satisfaction with the in-hospital practical training. Therefore, the aim of this study was to verify the validity of reviewing based on the questionnaire results by analyzing the data accumulated during the long-term practical training. A questionnaire survey was conducted of 333 5th-year students upon completion of practical training at Chiba University Hospital from 2010 to 2017. Students self-evaluated their attitude toward practical training on a 6-point scale and their satisfaction level for each component of the practical training on a 5-point scale. The students were also allowed to share their feelings about hospital pharmacy work. Repeated review of the training content can facilitate communication with patients, which was lacking at the beginning of the training period. Improved communication led to higher-quality pharmacy practice and increased student satisfaction. Meanwhile, changes to work procedures may reduce student satisfaction unless the training strategy is reviewed accordingly. Because the work of hospital pharmacists is constantly changing, it is considered that the content of the practical training should be revised accordingly through continuous conduction of surveys and evaluations, thereby enabling optimal practical training.

Pharmacokinetic Analysis of Intraocular Penetration of Latanoprost Solutions with Different Preservatives in Human Eyes.

PURPOSE: To investigate the effect of excipients on latanoprost penetration into the aqueous humor with clinically available 6 products with different solutions mainly in the types and concentrations of preservatives. METHODS: In 363 patients with cataracts, we instilled 1 latanoprost drop in 1 eye before surgery. The drop was randomly selected by brand name product (A) and 5 generic products (B-F) composed with different excipients. B contains similar excipients to A. C and D contain lower concentrations of benzalkonium chloride than A. E includes sodium benzoate, and F contains no preservatives. At 0.5-1, 3, and 6 h after instillation, samples of aqueous humor were collected to determine the latanoprost free acid by mass spectrometry. The time course of intraocular concentration and the areas under the aqueous humor latanoprost free acid concentration-time curves (AUCs) were calculated. RESULTS: At 0.5-1 h, the aqueous humor concentration of latanoprost free acid was 8.5 ± 1.0 ng/mL for C, which was significantly higher (P < 0.01) than that of A (3.4 ± 0.5 ng/mL). At 3 and 6 h, however, no significant difference was noted in the concentrations of latanoprost free acid between the brand name and generic products. For each of the generic products, the peak free acid concentration was above the known threshold concentration for biological activity. At 6 h postdose, however, the levels of latanoprost free acid were below the threshold for Products C, E, and F. Comparisons of AUC0-6h and AUC0-24h values showed that these parameters were the greatest with A, and E was significantly inferior to A (P < 0.05). CONCLUSIONS: Currently available latanoprost solutions with different preservatives showed sufficient intraocular concentration to activate the FP receptor, but different pharmacokinetic profiles of absorption or elimination.

In Practical Training, a Questionnaire Survey and Analysis to Pharmacy Students of the Utilization Situation of the Course Contents of Pharmacy School.

Pharmacy education comprises basic pharmacy (organic chemistry, biochemistry, and physical chemistry) and applied pharmacy (clinical pharmacy, pharm aceutics, and chemical hygiene). Students are expected to apply these subjects studied in pharmacy school during their practical pharmacy training. However, knowledge gained in university does not appear to be fully utilized in practice. We hypothesized that this is due to a lack of connection between pre-practical training education and actual practical training. Thus, we conducted a questionnaire study among pharmacy students to verify this hypothesis. We sent a questionnaire to 601 students in their sixth year of the pharmacy course at Chiba University, Teikyo University, or Kobe Pharmaceutical University who had undergone long-term practical training. The questionnaire asked about the utility of each subject of study and the reason for the judgement regarding the utility. Four hundred and forty-two students replied (response rate, 73.5%). A small proportion of students found the basic pharmacy subjects useful: physical chemistry, 5%; organic chemistry, 10%; and biochemistry, 24%. In contrast, more than half of the students found the clinical pharmacy subjects useful: pharmacology, 85%; pharmaceutics, 55%; pathophysiology, 75%; pharmacotherapeutics, 84%; and pharmaceutical regulations, 58%. Analysis of the comments left in the free-description section on the questionnaire revealed that most students did not have any opportunity to use their knowledge of the basic subjects during practical training, and furthermore, did not learn the processes involving the use of such subjects to solve clinical problems. Universities and pharmacists need to collaborate so that students can learn such processes.

Pharmaceutical studies of levothyroxine sodium hydrate suppository provided as a hospital preparation.

The levothyroxine sodium hydrate suppository (L-T4-suppository) is provided as a hospital preparation for the treatment of hypothyroid patients with dysphagia in Japan because only oral preparations of levothyroxine sodium (L-T4) are approved for the treatment of hypothyroidism. However, it has been found that serum thyroxine and triiodothyronine levels do not increase as expected with the hospital preparation, requiring a higher dosage of L-T4 in the L-T4-suppository than in the oral preparations. In this study, to determine an effective thyroid gland hormone-replacement therapy for patients with dysphagia, the pharmaceutical properties of the L-T4-suppository were investigated. Suppositories containing 300 µg L-T4 in a base of Witepsol H-15 and Witepsol E-75 (ratio of 1 : 1) were prepared according to Chiba University Hospital's protocol. Content uniformity, stability, and suppository release were tested. The L-T4-suppository had uniform weight and content. The content and release property were stable over 90 d when the L-T4-suppository was stored at 4 °C and protected from light. The release rate of L-T4 increased as pH increased. However, no L-T4 was released below pH 7.2. The release rate of L-T4 decreased as temperature decreased. These findings suggest that the low level of release of L-T4 in the rectum under physiological conditions may be the cause of the low serum thyroxine and triiodothyronine levels following L-T4-suppository administration.

Transition from positive to neutral in mutation fixation along with continuing rising fitness in thermal adaptive evolution.

It remains to be determined experimentally whether increasing fitness is related to positive selection, while stationary fitness is related to neutral evolution. Long-term laboratory evolution in Escherichia coli was performed under conditions of thermal stress under defined laboratory conditions. The complete cell growth data showed common continuous fitness recovery to every 2°C or 4°C stepwise temperature upshift, finally resulting in an evolved E. coli strain with an improved upper temperature limit as high as 45.9°C after 523 days of serial transfer, equivalent to 7,560 generations, in minimal medium. Two-phase fitness dynamics, a rapid growth recovery phase followed by a gradual increasing growth phase, was clearly observed at diverse temperatures throughout the entire evolutionary process. Whole-genome sequence analysis revealed the transition from positive to neutral in mutation fixation, accompanied with a considerable escalation of spontaneous substitution rate in the late fitness recovery phase. It suggested that continually increasing fitness not always resulted in the reduction of genetic diversity due to the sequential takeovers by fit mutants, but caused the accumulation of a considerable number of mutations that facilitated the neutral evolution.

Genetic materials at the gene engineering division, RIKEN BioResource Center.

Genetic materials are one of the most important and fundamental research resources for studying biological phenomena. Scientific need for genetic materials has been increasing and will never cease. Ever since it was established as RIKEN DNA Bank in 1987, the Gene Engineering Division of RIKEN BioResource Center (BRC) has been engaged in the collection, maintenance, storage, propagation, quality control, and distribution of genetic resources developed mainly by the Japanese research community. When RIKEN BRC was inaugurated in 2001, RIKEN DNA Bank was incorporated as one of its six Divisions, the Gene Engineering Division. The Gene Engineering Division was selected as a core facility for the genetic resources of mammalian and microbe origin by the National BioResource Project (NBRP) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan in 2002. With support from the scientific community, the Division now holds over 3 million clones of genetic materials for distribution. The genetic resources include cloned DNAs, gene libraries (e.g., cDNA and genomic DNA cloned into phage, cosmid, BAC, phosmid, and YAC), vectors, hosts, recombinant viruses, and ordered library sets derived from animal cells, including human and mouse cells, microorganisms, and viruses. Recently genetic materials produced by a few MEXT national research projects were transferred to the Gene Engineering Division for further dissemination. The Gene Engineering Division performs rigorous quality control of reproducibility, restriction enzyme mapping and nucleotide sequences of clones to ensure the reproducibility of in vivo and in vitro experiments. Users can easily access our genetic materials through the internet and obtain the DNA resources for a minimal fee. Not only the materials, but also information of features and technology related to the materials are provided via the web site of RIKEN BRC. Training courses are also given to transfer the technology for handling viral vectors. RIKEN BRC supports scientists around the world in the use of valuable genetic materials.

Cadmium transport by human Nramp 2 expressed in Xenopus laevis oocytes.

Using the Xenopus oocyte expression system, human Nramp2, a human intestinal iron transporter, was shown to work as a cadmium transporter. An 1824-bp human Nramp2 cDNA was constructed by PCR cloning from reverse transcription products of human kidney mRNA. When the pH of the extracellular solution was 6.0, human Nramp2 transported (109)Cd(2+). Substitution of external Cl(-) with NO3- had no effect on human Nramp2-dependent cadmium uptake. The concentration-dependent Cd(2+) transport of human Nramp2 indicated Michaelis-Menten type transport with an average K(m) value of 1.04 +/- 0.13 microM and an average V(max) of 14.7 +/- 1.9 pmol/oocyte/h (n = 3). Cd(2+) transport via human Nramp2 was inhibited significantly by Cd(2+), Fe(2+), Pb(2+), Mn(2+), Cu(2+), and Ni(2+), while it was not inhibited by Hg(2+) and Zn(2+). Transport of 0.1 microM Cd(2+) by human Nramp2 was inhibited by metallothionein (IC50 = 0.14 microM). Therefore, human Nramp2 is suggested to function as a pH-dependent cadmium absorption transporter on the luminal membrane of human intestinal cells.