Prostaglandins (PGs) are oxygenated derivatives of arachidonic acid, synthesized through sequential catalysis involving cyclooxygenase (COX) and PG terminal synthases. Of the two COX enzymes, COX-2 is induced by inflammatory and pro-carcinogenic stimuli and it not only promotes inflammatory reactions but it also plays a role in the development of various tumors. Nonsteroidal anti-inflammatory drugs (NSAIDs), which suppress inflammatory responses by inhibiting COX, have also been reported to suppress carcinogenesis in the colon. However, long-term use of NSAIDs for the prevention of cancer causes several side-effects; therefore, an alternative COX target is required. In this review, the role of PG synthases that are produced downstream of COX in carcinogenesis will be explained and novel drug targets to inhibit carcinogenesis will be discussed. Microsomal PGE synthase (mPGES)-1 and prostacyclin synthase (PGIS), which are coupled with COX-2 to generate PGE₂ and PGI₂, respectively, promote inflammation. In mPGES-1 knock-out mice, carcinogenesis in the colon, skin, and bladder were suppressed. As mPGES-1 deficiency does not result in abnormalities, mPGES-1 inhibitors are expected to be promising alternatives to NSAIDs for the suppression of cancer. On the other hand, it has been reported that PGIS suppresses colon cancer, suggesting that it has an opposite role to mPGES-1 in carcinogenesis in the colon. However, PGIS not affect carcinogenesis in the skin. These results suggest that PGIS has differential effects on carcinogenesis in different tissues.

Serotonergic neurons play a critical role in processing reward and aversive information. Rewarding stimuli activate serotonergic neurons in the dorsal raphe nucleus (DRN), whereas optogenetic activation of DRN serotonergic neurons induces reward-like effects. However, the pharmacological enhancement of serotonin neurotransmission does not induce rewarding or aversive effects. These findings suggest the presence of another serotonergic neuron that plays a role opposite to that of the DRN in processing reward and aversion information. Previous reports suggested that the median raphe nucleus (MRN) processes negative emotional stimuli. To elucidate the function of MRN serotonergic neurons in these processes, we recorded the changes in serotonergic activity in mice in response to rewarding and aversive stimuli. We also used optogenetic manipulation to determine whether these changes could induce rewarding and aversive behaviors. The activity of MRN serotonergic neurons decreased in response to rewarding stimuli and increased after aversive stimuli. Optogenetic inhibition of MRN serotonergic neurons induced reward-related behavior, while optogenetic stimulation induced aversion-related behavior. Furthermore, we found that the projection pathway from MRN serotonergic neurons to the interpeduncular nucleus is crucial for these processes. These results indicate that MRN serotonergic neurons play a pivotal role in processing reward and aversive information, functioning oppositely to DRN neurons.

Liquid chromatography tandem mass spectrometry (LC-MS/MS) is an essential tool for drug discovery that enables simple and rapid identification and quantification of chemical substances. A combination of a mobile phase and column makes it possible to analyze a wide range of target substances from low-molecular weight high-polar substances, such as amino acids and peptides, to low-polar substances such as lipids, and even macromolecular substances such as proteins. In this paper, we describe the results of applying LC-MS/MS to the analysis of phospholipids and related substances in biological samples and the analysis of photoproducts of pharmaceuticals. First, MS conditions were optimization using several standards, and a system that enables measurement of a vast number of molecular species with different carbon chain lengths and degrees of unsaturation. Its application to the lipid profiling of influenza A virus-infected cells suggested that viral infection triggered the increase of intracellular levels of diacylglycerols and ceramides at the later stages of infection concomitant with viral replication. In addition, the analysis of lysophospholipids in several cell lines revealed partial functions of several types of glycerophosphodiester phosphodiesterase, which metabolize lysophospholipids. Next, the chemical structures of several photoproducts of pharmaceuticals were elucidated. Novel photoproducts of photo-exposed pharmaceuticals were identified, and the photodegradation pathways were suggested. Based on the photodegradation mechanism, the photodegradability of naproxen was regulated by the addition of several additives such as polyphenols.

The implementation of antimicrobial stewardship (AS) is an important issue that pharmacists should promote through cooperation with physicians and other medical professionals. A core strategy for AS is "proactive intervention and feedback" on antimicrobial prescriptions. We evaluated the AS program to optimize antimicrobial chemotherapy in patients with positive blood cultures. For patients with bacteremia, the rate of bacterial disappearance significantly improved in cases in which the feedback based on the antimicrobial susceptibility testing results by the AS team was accepted than in cases in which it was not. Additionally, we attempted to conduct therapeutic drug monitoring for important antimicrobial agents, such as colistin (anti-multidrug-resistant Pseudomonas aeruginosa agent), vancomycin, daptomycin (antibiotics for methicillin-resistant Staphylococcus aureus), and voriconazole (antifungal drug), to optimize dosage and administration for efficacy and safety. For daptomycin, we found a correlation between plasma through concentration and musculoskeletal toxicity in a clinical study. Moreover, direct toxicity to human skeletal cells was observed in an in vitro study using human myoblast cultures. Overall, the results of these studies indicate that further clinical research on AS may aid the improvement of patient efficacy and safety.

Poor medication compliance in children can affect treatment efficacy. We examined the impact of a picture book created by pharmacists to improve medication compliance in children. Our study aim was to assess the effects of the pharmacist-created picture book on medication compliance in children and their parents in collaboration with an outpatient pharmacy. This study included 74 children [recovery rate 28/74 (37.8%)] aged 3-6 years and their parents between March 2023 and March 2024. In the item "Have you experienced any difficulties in giving medication to your child?" the proportion of respondents answering, "Always" or "Sometimes" decreased from 78.3% (18/23) to 34.7% (8/23) after reading the picture book (p<0.01). When answering the question "What specific situations have you found challenging when giving medication?" the number of responses decreased from (an average/mean) of 1.5 situations before reading the picture book to 1 situation. Regarding whether guardians felt a greater appreciation for the importance of giving medication to their children after reading the book, 64.3% answered "Yes," the highest response. A positive correlation (correlation coefficient=0.77, p<0.01) was observed between "Is the child interested in taking the medication?" and "Is the child able to take the medicine? Pharmacists need to raise public awareness of the importance of medication adherence. Since picture books are likely to be repeatedly read aloud, they are considered effective. The results of this study suggest that pharmacist-created picture books may contribute to improving medication compliance in children.

Blood purification therapy with cytokine-adsorbing hemofilters has been used to treat sepsis-associated hypercytokinemia. Polymethylmethacrylate (PMMA) hemofilters are frequently used for this purpose; however, adsorption and removal of teicoplanin, a therapeutic agent, have been reported. Similar concerns have been shared regarding daptomycin because its structure resembles that of teicoplanin; nevertheless, there have been no reported effects associated with daptomycin in this context. We studied the adsorption of daptomycin onto a PMMA hemofilter in vitro and investigated its adsorption onto hollow fiber membranes by adding cut PMMA membranes to a daptomycin solution. Additionally, the daptomycin solution was circulated in a dialysis circuit connected to a PMMA hemofilter, and changes in daptomycin content were examined. The daptomycin content decreased immediately after adding the hollow fiber membranes, similar to that observed for teicoplanin. The daptomycin content was lower than that of the standard reagent in the dialysis circuit model, reaching values below the measurement limit after 20 min. These results suggested that daptomycin was adsorbed and removed by the PMMA hemofilter. Encountering this effect during clinical use is plausible; therefore, daptomycin administration via a PMMA hemofilter should be avoided during blood purification therapy.

While decreased renal function is a known risk factor for hypermagnesemia caused by magnesium oxide (MgO), few studies have comprehensively investigated other contributing factors. In this study, the researchers analyzed the risk factors for hypermagnesemia development in 256 inpatients receiving MgO treatment at the Matsuyama Shimin Hospital. Multivariate analysis identified blood urea nitrogen ≧22 mg/dL, estimated glomerular filtration rate ≦43.1 mL/min, and MgO ≧1000 mg/d as risk factors. Additionally, the researchers' findings suggest a correlation between the number of risk factors and the incidence of hypermagnesemia, including the prevalence of Grade 3 cases. Interestingly, low body mass index emerged as a potential risk factor even in patients without the three identified factors. These findings highlight the importance for pharmacists to advocate for routine serum Mg level monitoring in patients with the risk factors identified in this study.

In Japan, the Pharmaceutical and Medical Device Act was amended in December 2019, and now requires pharmacists to follow-up on patients during treatment. Although there have been some studies on the effectiveness of follow-ups by pharmacists, there are no reports on the status of implementation in clinical practice. We conducted a nationwide survey on follow-up care to investigate the actual situation. We randomly selected 10% of community pharmacies in each prefecture and conducted a survey. We built a web-based system for the collection of basic information on the pharmacies and follow-up cases. A total of 561 pharmacies were pre-entered. Of these, 110 pharmacies (19.6%) reported 326 follow-up cases. Information was provided to doctors in 129 cases (39.6%), of which prescription proposals were made in 10 (7.8%) instances. The follow-up implementation rate based on the number of prescriptions dispensed was estimated to be 0.84% (95% confidence interval: 0.76-0.94%). This study revealed the status of follow-ups in clinical practice. Pharmacists can contribute to the optimization of drug treatment by providing follow-up information to doctors and making prescription proposals.

The Japanese package insert (J-PI) for nirmatrelvir/ritonavir (N/r) (specially approved pharmaceutical) includes numerous warnings about drug interactions. However, discrepancies in the information on drug interaction are reported between J-PI and foreign databases. This study aimed to evaluate various information sources on N/r drug interactions. We categorized and compared information on N/r drug interactions from the J-PI, prescribing information from foreign regulatory agencies, guidance from the National Institutes of Health and University Health Network, the Ontario coronavirus disease 2019 (COVID-19) Science Advisory Table, University of Liverpool, Lexicomp, and the Japanese Society of Pharmaceutical Health Care and Sciences (JSPHCS). We assessed information quantity, missing data in J-PI, predicted change of the area under the blood concentration-time curve (AUC) for nirmatrelvir or co-administered drugs, and the information source consistency. From these information sources, we compiled a dataset with 115 contraindications and 203 precautions for N/r co-administration, and 51 contraindications are missing in J-PI. Among them, at least 12 drugs have large predicted AUC changes with N/r (AUC ≥5-fold or <1/5 of the baseline value). Nine of these 12 drugs are included as contraindications in Lexicomp and the JSPHCS. The consistency among the information sources is low. Information in the J-PI alone may be insufficient and Lexicomp or the JSPHCS guidelines should be useful because of their large amounts of information and wide coverage of drugs with large AUC changes. Due to low source consistency, multiple sources are needed for clinical management.

In 2020, the Japan Community Healthcare Organization (JCHO) Hoshigaoka Medical Center started providing information to community pharmacies about patients admitted to the acute care ward using discharge medication summaries (the summaries). We conducted an online self-recording survey of 149 pharmacies belonging to the Hirakata City Pharmacists Association to clarify the usability of the summaries, any related issues, and to further discuss future collaboration between hospitals and pharmacies. 46 pharmacies have received the summaries in the past, of which 44 pharmacies answered that they have utilized the summaries with patient instruction and prescription queries of doctors. However, two pharmacies responded they did not utilize the summaries, and the reasons were (a) the information was not timely and (b) patients whom the discharge medical summary was sent for did not come to the pharmacy. There were some requests regarding the summaries such as, “I would like to know what kind of information hospital pharmacists want from community pharmacists.” Preference for sharing information other than the summaries (e.g., online tools) with hospital pharmacists was related to whether the pharmacy was providing home pharmaceutical visit services. The survey revealed that, in addition to the usability of the summaries, there are also events that prevent them from being utilized. Some of the challenges include the timing of sending the summaries, the accurate identification of the family pharmacy and the communication of follow-up after discharge from hospital. Collaborating with pharmacies providing home pharmaceutical visit services would be beneficial in creating new system of bidirectional information sharing.