This review, based on my research work, introduces and summarizes the synthesis and characterization of novel cyclic compounds containing aminobenzenesulfonamide. The review discusses the (1) development of sequential Nicholas and Pauson-Khand reactions for the synthesis of unique polyheterocyclic compounds, (2) production of 2-aminobenzenesulfonamide-containing cyclononyne (ABSACN) as a multifunctional click cycloalkyne agent, and (3) improvement of the intramolecular Pauson-Khand reaction of the nitroarene-enyne substrate for the synthesis of cyclopenta[c]piperidine alkaloids. This research work will facilitate the discovery of sulfonamide or sultam-based functional molecules and pharmaceuticals. Thus, I believe that aminobenzenesulfonamide derivatives are versatile and valuable chemical moieties not only in organic syntheses but also in the pharmaceutical industry. If you are interested in the details of this topic, please refer to the original papers.

The lens of the eye is an avascular and anuclear tissue that serves to focus objects on the retina. Cataract is opacity within the clear lens that changes the transparency and refractive index of the lens causing significant visual impairments. These impairments can severely restrict the ability to carry out daily activities. Cataracts is common among elderly person occurring in more than 80% of patients aged 80 or older. Notably, we have recently identified key compounds that are effective against cataract formation. Presbyopia is also an ocular disease that typically develops in people over the age of 45 while affecting almost 100% of people over the age of 65. Recent research suggests that age-related changes in hydrostatic pressure of the lens controlled by Na/K ATPase contribute to the development of presbyopia. In the lens, Na/K ATPase has been shown to be regulated by transient receptor potential cation channels, vanilloid 1 (TRPV1) and 4, thus suggesting the potential role of TRPV1 and TRPV4 in the development of presbyopia. This review article summarizes data obtained from our laboratory with my colleagues highlighting the critical role of aquaporin 0 (AQP0) in maintaining a healthy lens redox environment, key molecules that delay the onset of cataract in vivo, as well as potential mechanisms of lens hydrostatic pressure control that may be associated with presbyopia.

Organoselenium compounds have attracted significant interest because of their use as important reagents in organic syntheses and potential biological activities, necessitating the development of simple and general synthetic methods. This article reviews our studies to develop of copper-catalyzed C-Se bond formation reactions via cross coupling and C-H activation. A number of unsymmetrical and symmetrical diaryl selenides were synthesized via Se-arylation of diaryl diselenides or selenium powder with triarylbismuthanes under aerobic conditions, achieving moderate to excellent yields. When the reaction of triphenylbismuthane with elemental Se was monitored with gas chromatography, diphenyl diselenide and diphenyl selenide formation was confirmed. Subsequently, 1-pot 2-step reactions were performed under mild conditions to obtain 3-selanyl imidazo[1,2-a]pyridines from triarylbismuthanes and diimidazopyridyl diselenides, which were generated from imidazo[1,2-a]pyridines and Se powder, in good to excellent yields. It should be noted that all three aryl groups in the bismuth and both selanyl groups in the diaryl diselenide generated from the selenium source were transferred to the coupling products. Cu-catalyzed tandem cyclization of 2-(2-iodophenyl)imidazo[1,2-a]pyridines with selenium for the synthesis of benzo[b]selenophene-fused imidazo[1,2-a]pyridines is also described herein. The molecular structure of the tetracyclic compound features nearly coplanar rings, and the maximum absorption is red-shifted compared to those of imidazo[1,2-a]pyridine and benzoselenophene.

The true central aim of pharmaceutical research and education is to strive for the patient's satisfaction, i.e., “for the sake of the patient”. Our research focuses to bridge the gap between the ideal and current situation in pharmaceutical science. We also investigated/questioned the united roles of pharmacists and pharmacies, with the ambition of changing the work culture of pharmacists. This paper reviews the history of our research and discusses the future of pharmaceutical research and education.

Humans are exposed to various xenobiotic electrophiles on a daily basis. Electrophiles form covalent adducts with nucleophilic residues of proteins. Redox signaling, which consists of effector molecules (e.g., kinases and transcription factors) and redox sensor proteins with low pK_a cysteine residues, is involved in cell survival, cell proliferation, quality control of cellular proteins and oxidative stress response. Herein, we showed that at a low dose, xenobiotic electrophiles selectively modified redox sensor proteins through covalent modification of their reactive thiols, resulting in activation of a variety of redox signaling pathways. However, increasing the dose of xenobiotic electrophiles caused non-selective and extensive modification of cellular proteins involved in toxicity. Of interest, reactive sulfur species (RSS), such as hydrogen sulfide (H₂S), cysteine persulfide (CysSSH), glutathione persulfide (GSSH) and even synthetic polysulfide (e.g., Na₂S₄), readily captured xenobiotic electrophiles, forming their sulfur adducts, which was associated with inactivation of the electrophiles. Our findings suggest that an adaptive response through redox signaling activation and RSS-mediated electrophile capturing is involved in the regulation of electrophilic stress.

The medical information and communication technology “Kibitan Health Net” was introduced as a part of the medical reconstruction assistance national project in Fukushima. However, its effect on the performance of the pharmacists has not yet been validated in community pharmacy. In this study, we investigated the usefulness of acquisition and utilization of precise medical information from diabetic patients using Kibitan Health Net. The subjects of this study were 18 patients having type 2 diabetes mellitus with a mean HbA1c level of 7.4±1.0 (%). We compared the HbA1c level captured by the pharmacists from the patients (total 72 times) with that updated on Kibitan Health Net (41 times correctly captured by the pharmacists). We next compared the HbA1c levels between the “group that could listen to accurate laboratory data” and the “group that could not listen to accurate laboratory data” using intergroup analysis. After factor analysis between the two groups, we demonstrated that the proportion of patients who could not precisely communicate laboratory results was significantly higher among the elderly population (p<0.05). Recent studies have reported that elderly diabetic patients have a higher risk of cognitive decline and Alzheimer-type dementia resulting in higher brain dysfunction. The utilization of Kibitan Health Net enabled the capturing of precise patient information. These data could make it possible to provide instruction for proper compliance and guidance for recuperation among the elderly diabetic patients, and prevent their cognitive decline due to poor glycemic control, as well as set future therapeutic goals and improve adherence.

Osteoarthritis is the most common joint disorder worldwide and one of the leading causes of disability in the elderly. We have reported that the novel sodium hyaluronate derivative chemically linked with diclofenac (DF), diclofenac etalhyaluronate (SI-613), exerted a potent and long-lasting analgesic effect in experimental arthritis models. In this study, we evaluated the properties of residual SI-613 in the knee joint after an intra-articular (IA) administration. After IA administration of fluorescent labeled SI-613 (FA-SI-613) or fluorescent labeled hyaluronic acid (FA-HA) to rabbits, fluorescence intensities in the synovial membrane and cartilage were higher in the FA-SI-613 group until 7 d after administration than in the FA-HA group. After IA administration of radiolabeled SI-613 (¹⁴C-SI-613) to rabbits, the radioactivity remained in the joint cavity and the joint tissues such as synovial membrane and cartilage until 84 d after administration. This residual radioactivity was identified mainly as HA linked with DF, since ¹⁴C-SI-613 was labeled at the benzene ring of DF and since more DF-linked HA oligomer was detected on metabolite analysis than free DF in the synovial membrane and synovial lavage fluid up to 28 d after administration. These results suggested that intra-articularly administered SI-613 remained for a longer time in the joint as HA linked with DF than when HA was administered. Therefore, SI-613 was considered to prolong the pharmacological effects of both HA and DF by remaining in the joint as HA linked with DF.

Pharmacists working in collaboration with doctors are mainly involved in proposals and inquiries of prescription. At such times, belief conflicts are expected to deteriorate teamwork and induce stress. However, there is no strong evidence for this. To clarify factors resulting in belief conflicts, we conducted a survey among 594 pharmacists working at medical institutions in Gifu City and belonging to Gifu Pharmaceutical Association or Gifu Prefectural Society of Hospital Pharmacists between January 2019 and April 2019. The items of the survey were gender, place of employment, pharmacist working experience (years), awareness of “professional competencies for pharmacists” stated in Model Core Curriculum for Pharmacy Education —2015 version—, whether each item of “professional competencies for pharmacists” is applicable to himself/herself or not, whether teamwork deteriorates and stress occurs due to proposals and inquiries of prescription or not, and Assessment of Belief Conflict in Relationship-14 (ABCR-14). The recovery rate of the questionnaire was 50.3% and the valid response rate was 77.6%. Multiple logistic regression and Bayesian network analyses revealed that “I can empathize with a patient's feelings and emotions, but I experience difficulty with unfair criticism” commonly resulted in teamwork deterioration due to proposals of prescription. “Pharmacist working experience years (more than 10 years)” and “The other staff make unreasonable demands of me in the work” commonly resulted in stress. Thus, belief conflicts in therapeutic relationships result in teamwork deterioration and stress in prescription proposals.

Relationship between water molecules and parent and hydroxypropylated cyclodextrins (denoted as CD and HP-CD) was assessed in this paper. The trends in ad-desorption isotherms of CD for water molecule were quite different compared to those of HP-CD. Ad-desorption isotherms of CD showed the hysteresis under our experimental conditions. The molar ratio of hydration (R-value) using α-CD, β-CD, γ-CD, HP-α-CD, HP-β-CD, and HP-γ-CD was 7.1, 11.4, 13.5, 12.5, 14.0, and 16.7, respectively. These results indicated that the adsorption capability of water molecule of HP-CD was greater than that of CD. Additionally, the changes in characteristics of CD and HP-CD at different water activity conditions were demonstrated. X-ray diffraction patterns were significantly different between CD and HP-CD. The crystal structure of HP-α-CD, HP-β-CD, and HP-γ-CD showed amorphous at different water activity conditions. Finally, sorption entropy and heat of sorption of water molecules were calculated in this experiment. In summary, these results provide useful information for understanding the relationship between water molecules and parent and hydroxypropylated cyclodextrins.

The mock patches were prepared with novel acrylic polymers as adhesive layer where biphenyl-4-ylacetic acid (BAA) or 2-(2-fluorobiphenyl-4-yl) propanoic acid (FPA) was used as model active pharmaceutical ingredients (APIs). In addition, the mock patches were formulated with typical ester ingredients for transdermal dosage forms. The molecular state of the model APIs in the adhesive layer was observed by polarized microscope and microscopic Raman spectroscopy, which contains both conventional and low frequency (LF) region. Crystallization behavior would be depended on the interaction between API and polymers in the adhesive layer. In particular, LF Raman measurement was useful to discriminate API polymorphs. The pharmaceutical properties including dissolution and skin permeation of APIs were also evaluated for mock patches. The drug release and transdermal permeation were enhanced with the ester ingredients such as isopropyl myristate and diethyl sebacate due to their diffusion to the test solution or the skin stratum corneum as well as reducing the interaction between API and polymers. Further, the tack strength was not changed, but the peel strength was weakened by the additives. Thus, the adhesive properties were controllable by formulation with the additives. These findings could enable to evaluate the interaction between API and the polymers for adhesive layer and select the appropriate polymer and additives for used APIs when designing the drug products.

Lipid lowering therapy using statins prevents the risk of cardiovascular events. However, since the year 2000, there have been some reports that statins increased the risk of developing diabetes (SIRDD). It is socially demanded that pharmacists must apply pharmacotherapy to patients by utilizing drug information like the above, such as selecting appropriate drugs and providing correct drug information. Accordingly, pharmacists must correct drug information, and they should analyze and evaluate such information. Therefore, we conducted a questionnaire survey for pharmacists in community pharmacies with an aim to verify relevance between methods of obtaining drug information and the utilization of the information of “SIRDD” as a subject. We sent a questionnaire by letter to 1522 pharmacists in Fukushima and Mie prefecture, and received the results of the questionnaire from them using “Google forms” that is software to make web questionnaire and letters. We obtained responses from 356 (23.4%) pharmacists out of 1522. The number of responses from the pharmacists that “know” the information of “SIRDD” was 135 (37.9%). We found that these pharmacists obtained the information by websites of pharmaceutical companies, m3, Inc. (Portal site for medical professionals), and Pharmaceuticals and Medical Devices Agency (PMDA), as the sources of information. Our results suggested that pharmacists responded that they “know” “SIRDD” utilized websites as a quick information tool. The difference in network environments will relate to the difference of providable medical quality. So, it is very important to maintain appropriate network environment in cooperation with medical institutions, professional associations and the government.

The purpose of this study is to understand the reading habits of Japanese pharmacists regarding clinical trial literature in 2014. Questionnaires were mailed to 1997 pharmacists in Miyagi Prefecture. Six hundreds and five [342 (56.5%) hospital pharmacists and 254 (42.0%) community pharmacists] responded to questionnaires (Response rate: 30.3%). Regarding the question, “Do you habitually read clinical trial literature?”, 19.5% of hospital and 8.3% community pharmacists responded “yes”, respectively, which showed both pharmacists are not habitual readers of clinical trial literature. That would be because they did not study critical reading of clinical trial literature at pharmacy schools as well as their work environments to access and retrieve clinical trial literature were limited.