Tissue barriers contribute to the maintenance of homeostasis in the body, and tissue barrier dysfunction presents a risk factor for a variety of diseases. The blood-brain barrier (BBB) is a major tissue barrier acting as a static barrier and dynamic interface that plays an important role in the maintenance of central nervous system homeostasis. We show the functional characterization of the brain-to-blood efflux transport system of amyloid-β peptide (Aβ) across the BBB. We found that activated vitamin D3 may be a candidate agent for modulating the Aβ clearance across the BBB. Cerebral creatine deficiency syndromes are caused by loss-of-function mutations in the creatine transporter (CRT; SLC6A8), which transports creatine at the BBB. We found that functional impairment of CRT due to a G561R mutation resulted in incomplete N-linked glycosylation due to misfolding during protein maturation, leading to impaired creatine transport activity at the BBB. To develop a delivery system for biomedicine across the tissue barrier, we established a screening system to identify cell-penetrating peptides by a combination of in vitro cell permeability screening assays and phage display technology. Using this system, we identified cyclic hepta-peptides that are able to facilitate intestinal absorption of phages in vitro and in vivo, which are promising candidates as a carrier for macromolecular biomedicines. In conclusion, these studies focusing on the dynamic interface of tissue barriers will contribute to knowledge on disease pathogenesis as well as the development of a targeted biomedicine delivery system.
Comprehensive identification of antigens in immune complexes (IC-antigens) is beneficial to provide insights into pathophysiology and could form the basis for novel diagnostic and treatment strategies for many immune-related diseases. Immune complexome analysis is a method for comprehensively identifying and profiling IC-antigens in biological fluids (such as serum and cerebrospinal fluid). We applied this strategy to the analysis of circulating ICs in autoimmune diseases (rheumatoid arthritis, Sjögren's syndrome, systemic scleroderma, and systemic lupus erythematosus), infectious diseases, and cancers. Fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) consists of fluorogenic derivatization of proteins, followed by HPLC of the derivatized proteins, isolation of the proteins differentially expressed in a certain group, enzymatic digestion of the isolated proteins followed by LC-tandem MS using a database-searching algorithm for protein identification. We have applied this method to understand the cardioprotective effect of pre-administration of docetaxel in adriamycin/docetaxel combination anti-cancer therapy, and the cellular processes that are affected by non-steroidal anti-inflammatory drugs (NSAIDs) in mouse stomach tissue during ulcer formation.
The town of Anamizu in Housu District, Ishikawa Prefecture, in the northern part of the Noto Peninsula, has 8600 residents of whom 45.4% are 65 years or older, making it a region with an aging population. A project was launched to “make Anamizu a town known for the good health and long life” of its citizens. The project involved, among other things, health classes run by health outreach workers. The local government of Anamizu enlisted the participation of local pharmacists, by requesting that the Anamizu group of the northern Noto chapter of the Ishikawa Prefecture Pharmacists Association (comprising seven pharmacies) conduct health classes. The pharmacies within the specified group collaborated to hold 17 classes in 17 areas within six months, starting from October 2016. They conducted the health classes and held periodic meetings to confirm class topics and to standardize the responses to questions from the participants. In all, 258 residents joined the health classes, and the Anamizu pharmacist group received requests to hold more classes in 2017, based on positive feedback. The strong relationship among the pharmacies in the Anamizu group was one factor in the success of this project, executed in cooperation with the Department of Health Promotion. The shared goals of the pharmacies while tackling various projects—for example, in running a booth representing the Anamizu group at health festivals—enhanced their collaborative activities. The Anamizu group plans to conduct various other community activities in the future to improve the QOL of local residents.
Recently, we considered the term ‘integrated community care system’ and aimed to play a role in the process by joining various healthcare occupations as part of this new integrated system. Given our company's ties with people involved in a range of occupations, we are poised to play a liaison role. We called a “face-to-face meeting” with local healthcare practitioners to begin exploring this cooperation. We believe that as meetings such as these become more widespread across the Kinki Region, they can serve as part of an integrated community care system. Through the formation of a number of alliances by this means, we hope to facilitate the transition to an integrated community care system. The meetings will provide opportunities for a range of healthcare and long-term care professionals, such as physicians, pharmacists, care managers, social workers, and home-visit nurses, to engage in discussions centered on the interests and needs of patients. Another important topic is whether we can derive from these conversations efforts that would assist in the development of “health support pharmacies”. In that regard, we have set up some support tools for pharmacies that have held health fairs for local inhabitants. We consider these meetings beneficial in finding a solution to the situation of “polypharmacy”—a recent medical problem. We hope that our meetings will create an opportunity to work cooperatively toward a vision for the future of healthcare and long-term care within a community, through communicating and sharing our proposals for pharmacists based on these experiences.
About two years have passed since the formal establishment of the category “family pharmacist” in Japan's revision of dispensing fees. In the pharmacy vision for patients, many problems were raised among the category of “family pharmacists” or “family pharmacies”. Furthermore, in the future restructuring of pharmacy practices, by 2025 all pharmacies are to serve as “family pharmacies”, and by 2035 they will exercise their family pharmacy function in daily living areas. In order to demonstrate the “family function”, home medical care and outreach type health support etc. will be required, not only from conventional pharmacy work but also in outside (off-site) pharmacy activities. Therefore, future pharmacies need to gain the confidence of their local communities, such as in active collaboration with multi-occupational physicians and healthcare providers, work with multi-occupations in general, participation in local activities, and so on. Therefore, I would like to introduce activities that I am actually doing to this end, such as at-home activities, community activities and cooperation with multiple occupations.
The primary pharmacy system and health support pharmacy system were established in 2016. However, local pharmacies need to get closer to the community. To this end, each pharmacy is making efforts to contribute locally. Here, we introduce various initiatives in our region. Akakabe Pharmacy has 66 stores in Osaka Prefecture, mainly in the northeastern part of Osaka, where the elderly population is growing. We are implementing a dominant strategy: cooperation with the city and administration is strong, and we hold many related events directed towards the public. For example, two thousand participants gathered in an event sponsored by the city aimed at the improvement of beauty and health. At such events, participants can easily consult with pharmacists. Dispensing pharmacy stores—pharmacies that combine the features of a convenience store with care consulting services—were established in 2016. Care consultations are potentially highly advantageous to the users. In the consultation space of a pharmacy, a care worker conducts various events every month, such as on dementia prevention, body composition measurement, and more. We believe that this type of combined pharmacy and convenience store has the potential to become a regional comprehensive care center. We intend to share the possibility of a new pharmacy system, centered on this pharmacy/store/consultation model, as a basis to revamp the pharmacy industry.
We have conducted health promotion workshops in Kobe City, beginning in June 2016, to promote the view of pharmacies as community health centers that provide not only medicine but also offer support for maintaining and enhancing a person's health. To this end, we collaborated with Kobe Women's University (KWU). Our health promotion workshops included: 1. Activities of daily living (ADL) exercises led by a KWU professional; 2. Lectures on various diseases by dietitians and pharmacists; 3. Nutritional guidance from a dietitian; 4. Health counseling by a pharmacist; and 5. Measurements of bone density, vascular age, and so on. A significant portion of the participants were relatively healthy and had strong legs. In October 2017, we investigated changes in the participants' awareness about health through a questionnaire study. We analyzed the results of 26 individuals who participated in the workshops more than once—18 of them (69%) expressed increased interest in exercise, 15 (58%) had begun walking regularly, and 11 (42%) changed their diet in terms of dietary fiber and salt. This suggests that our health promotion workshops brought about positive changes in people with regard to awareness of health and a healthy lifestyle. To further explore how pharmacies might contribute to healthy life expectancy, we will continue to investigate the relationship between changes in exercise and diet and people's awareness of health. As a group exercise, from now on we have decided to expand the role of pharmacies as community health promotion centers with the slogan “Extend healthy life expectancy by having fun”.
For becoming a talented pharmacist at a health support pharmacy, the practitioner must obtain ability in two significant skill sets: “Technical skill” and “Non-technical skill”. Technical skills are that required for a pharmacist's specialty/expertise, such as a wide variety of specialized knowledge and techniques. Non-technical skills are those required for effective communication and cooperation with patients, as well as with professionals from multiple fields, and also leadership/problem-solving ability within a team. Therefore, technical skill and non-technical skill go hand-in-hand like the two wheels on an axle. In a community-based integrated care system, medical professionals are expected to support a patient's overall health more effectively, even extending into his/her private life. In order to enable pharmacists to expand their scope of activity and fully execute their expertise, Yakugaku Seminar Lifelong Learning Center supports pharmacists from the standpoint of education with various themes, for example: the simulated experience of doctor conducting patient education and formulation on a daily basis, learning a basic way of thinking when clinical decisions are made for a patient nearby, mature decision making by combining vital signs, communication that takes into consideration a patient's background, and improved communication or problem-solving abilities within a broader team.
The “Choosing Wisely” campaign is an activity to promote conversations between patients and doctors about unnecessary examinations, treatments, or procedures. A “Top five list” published by a number of specialty societies consists of five evidence-based recommendations in their own fields. Choosing Wisely Japan was launched in 2016; the campaign soon became widespread among primary care physicians. To make wiser choices in prescriptions of any medicine, it is necessary to consider the balance between its efficacies, risks, and costs. The purpose of this campaign is not only to publish recommendations to reduce waste in health care resources but also to disseminate and implement the recommendations contents. To put them into practice, it is necessary to think about interprofessional and interdisciplinary approaches.
Choosing Wisely (CW) is a pharmaceutical campaign activity that is spreading rapidly internationally. Briefly, it is an activity “aiming for appropriate medical care by reviewing the medical practice that is practiced despite lack of evidence from the viewpoint of evidence based medicine (EBM)”. Here, healthcare workers and patients, through dialogue, are aiming to be able to carry out medical practices (examinations, treatment) that are scientifically validated, truly necessary, and have few side effects. In 2012, the American Institute of Internal Medicine listed five topics (Top Five Lists) and presented the medical practices and reasons that should be reconsidered. Based on this, many academic societies and medical professional organizations around the world presented five unique lists from their respective standpoints. And, in 2016, CW Japan was established in our country. The ultimate goal of this activity is to encourage dialogue and share decision-making with the patients so that healthcare workers can “select wisely” appropriate medicine for their patients based on professionalism. In Japan, recent attention has also been paid to problems concerning proper use of polypharmacy and antibiotics, especially for elderly people. To support a sustainable medical system in the future, it is desirable to promote efforts to realize “high-value care” for patients, paying particular attention to limit unnecessary medical care. Under such circumstances, I will introduce some issues and activities that overseas pharmacists are working on in the context of CW, and discuss roles and tasks to be taken by pharmacists in Japan.
Antimicrobial resistance (AMR) has been declared a global public health emergency, necessitating the involvement of the whole of society to address this increasingly serious threat. AMR causes prolonged illness, greater risk of infection spread, increased morbidity, and higher mortality rates, which result in increased expenses to the government, healthcare services, and individuals. Inappropriate use of antimicrobials has been indicated as the primary cause for the global expansion of AMR. Under these circumstances, various countries have formulated suitable national action plans to curb AMR. In Japan, the national action plan on AMR was announced in April 2016. Our previous study clarified that orally administered antimicrobials accounted for approximately 90% of total consumption: oral third-generation cephalosporins, macrolides, and fluoroquinolones accounted for approximately 77% of oral consumption. Therefore pharmacists must extend their support for the appropriate use of antimicrobials prescribed by attending physicians to not only hospitalized patients but also outpatients. “Choosing wisely,” a US-based health education campaign, warns against unnecessary use of antimicrobials. Pharmacists should strive to disseminate the concept of “choosing wisely” in relation to other medicines, implement further interventions, and evaluate them. In this article, we present data on use of antimicrobials in Japan, and mention how pharmacists should be involved in enabling physicians choose antimicrobials wisely.
When considering the use of pharmaceutical drugs during pregnancy and lactation, two concerns must be weighed against each other: the potential deleterious effects on the fetus and the possibility that treatment necessary for the woman but risky for the fetus either cannot be administered or else the woman must give up the pregnancy or give up nursing. The main roadblock to weighing these two concerns is a lack of evidence about what drugs are harmful to the fetus. Establishing this evidence is important to implementing the “Choosing Wisely” policy. In 2005, Japan established the Japan Drug Information Institute in Pregnancy (JDIIP), which addresses issues regarding treatments with pharmaceutical drugs during pregnancy and lactation. The JDIIP has analyzed data regarding the pregnancy results of patients who have received counseling and has conducted a registration survey, analyzed post-marketing survey data from pharmaceutical companies, and measured drug concentrations in breast milk. Currently, the JDIIP is increasing the number of targeted drugs about which it is collecting evidence. In addition, it is re-evaluating the published literature and implementing a project to revise drug packaging inserts. Pharmacists are expected to implement the “Choosing Wisely” policy regarding pharmaceutical treatment during pregnancy and lactation and to contribute to the collection of new evidence.
In Japan, the population aged 65 years and older exceeds 28% of the total population. Since the birth rate is also declining, aging of the population is likely to continue. According to a patient survey conducted by the Ministry of Health, Labour and Welfare in 2014, the number of outpatients aged ≥65 years was higher by approximately 1.8 million since the previous survey in 2011. Drug therapy for the elderly is, thus, a matter of rapidly growing importance. The older generation has poorer physiological functions than younger adults. Therefore they are more likely to experience variable efficacy of drugs administered. The incidence of adverse effects is known higher in elderly people, and multidrug regimens are often unavoidable, especially when patients have more than one disease. In elderly patients, chronic lifestyle-related diseases are usually associated with geriatric syndrome. Given these circumstances, the potential area to be covered by pharmacists is very broad, and they should be involved in drug treatment of elderly people from hospital to home. We therefore propose the establishment of a new scientific field of geriatric pharmacology. We will consider novel approaches to geriatric pharmacotherapy from the viewpoints of basic science and clinical practice, deliberating the role that pharmacists should play in the provision of polypharmacy in older patients.
“Choosing Wisely” is a campaign activity promoting awareness of the dangers of providing medical tests, drugs, and procedures that are not supported by firm scientific evidence and that may harm patients. The American Society of Health-System Pharmacists has released a recommendation on polypharmacy. Stakeholders such as patients, health professionals, hospital executives, industry, and mass media may all contribute to treatment decision making. The patient-centric “five questions you need to ask your doctor” are a useful trigger for better dialogue between patients and health professionals and could contribute to appropriate drug prescription in which benefit always exceeds the potential for harm.
In this review, we focus on our recent work on the development of novel helical foldamers based on the cis conformational properties of aromatic amide bonds. First, we describe the conformational properties of N-alkylated pyrroleamides and their oligomers. The conformation of the amide bond on the pyrrole ring is altered by N-alkylation, and the ratio of the cis conformer is lower in N-methylated amides with an N-pyrrole ring compared with that in N-methylbenzanilide. Pyrrole-containing oligomers, in which benzene and pyrrole rings are linked alternately by amide bonds with chiral N-substituents, show significant CD signals that depend on the chain length, temperature, and solvent properties, indicating that the oligoamides take folded conformations in solvents. Second, we describe the design and synthesis of alternately N-alkylated aromatic oligoamides as novel helical oligoamides with larger cavities compared with those of poly(N-alkylated p-benzamides). Spectroscopic studies and calculated optimized structures indicate that these oligoamides adopt helical structures with a cavity of about 9 Å in diameter. Finally, we describe the synthesis of a series of strained aromatic oligoamide macrocycles based on the cis conformational preference of the aromatic N-alkylated amide bond, building on the work of Huc et al. on the construction of large macrocycles by cyclization of helical quinoline oligoamides. The crystal structures are also presented. Our findings demonstrate that N-alkylated amides with the cis conformation are useful building blocks for unique aromatic foldamers.
New meta-arylene ethynylene foldamers were developed by employing pyridine and phenol units. These demonstrated interesting properties related to the hydrogen-bonding behavior of the arylene units. Pyridine-acetylene-phenol foldamers showed improved saccharide recognition abilities compared with pyridine-acetylene foldamers with no phenol units. Solid-liquid extraction could be achieved due to the strong binding. Hydrocarbon stapling by alkene metathesis under templation was attempted, and the helical structure was efficiently stabilized. Phenol-acetylene oligomers spontaneously formed helical structures via intramolecular hydrogen bonding. The helical sense could be biased by adding chiral amines.
α,α-Disubstituted α-amino acids (dAAs), in which the α-hydrogen of the α-amino acid is replaced with an alkyl substituent, stabilize peptide secondary structures and have been utilized as a tool for building blocks of peptide foldamers. Peptides composed of acyclic dAAs with two bulky substituents equal to or larger than ethyl groups are more likely to form an extended planar conformation, whereas peptides with cyclic dAAs are more likely to adopt a helical structure. Based on these conformational properties of dAA-containing peptides, we developed a novel methodology using cyclic dAAs with an acetal side chain for conformational changes in peptides from a helical to a random structure with acidic treatment. Furthermore, peptide foldamers containing dAAs are useful for the design of functional peptides. In addition to the stabilization properties of peptide secondary structures, peptides foldamers exhibit resistance to degradation by proteases and thus are expected to be useful for development into bioactive peptides. In this presentation, I introduce cell-penetrating peptide foldamers as an application for dAAs in functional peptides. Peptide foldamers with appropriate functional groups at target positions show excellent, continuous cell membrane permeability and the ability to deliver biomacromolecules, such as plasmid DNA, into cells efficiently.
Diseases of the motor-conducting system that cause moving disability affect socio-economic activity as well as human dignity. Neurolathyrism, konzo, and amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC) have attracted researchers to study the pathology of motor neuron (MN) diseases such as ALS. I have been studying neurolathyrism, which is caused by overconsumption of a legume grass pea (Lathyrys sativus L.). Among people who consume the legume as a food staple, many developed life-long paraparesis in their legs. β-N-oxalyl-l-α,β- diaminopropionic (l-β-ODAP; BOAA), contained in this plant, is a neurotoxic analog of l-glutamic acid. We have clarified that in addition to the causal involvement of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamatergic receptor in MN death, a toxic role of group I metabotropic glutamate receptors as well as transient receptor potential channels were involved in the MN insult by l-β-ODAP using primary MN culture. We have also established a neurolathyrism rat model by repeated, peripheral l-β-ODAP treatment to newborn rats under mild stress. Rats showing hind-leg paraparesis with an incidence rate of around 25% were useful to study the in vivo pathology of MN disease. MNs of these rats were greatly decreased at their lumbo/sacral segments at various ages. Intra-parenchymal hemorrhage was consistently observed in paraparetic rats but not in cripple-free, treated rats. MN were depleted even at an acute period around bleeding spots, suggesting catastrophic neuro-vascular-glial interaction in this MN disease. Summaries of konzo and ALS-PDCs studies are also introduced.
Salmonella is a Gram-negative [Gram(−)] bacteria, distributed widely in such natural environments as soil, dust, or river water, causing food poisoning as well as oral infections such as Typhi or Paratyphi. Salmonella is highly tissue invasive, easily spreading throughout the whole body after initial growth in the phagocytic vesicles of macrophages as an intra-cellular parasite. Because there remain many unknown elements in the Salmonella-macrophage interaction, I started my study by focusing on the molecules and mechanisms underlying the interaction; for example, how Salmonella escapes natural biodefense systems armed by macrophages, and how macrophages surround and inactivate Salmonella. In addition, I developed insight into Salmonella survival in the face of both environmental stresses and immunological stresses, including attacks from macrophages, based on the idea that “pathogenicity” is not limited simply to an attack, but to both the attack and defense against hazards. In this study, I found a novel pathogenicity-related protein of Salmonella, SEp22, an iron-chelating protein of MW 18.7 kDa, to cope with reactive-oxygen intermediates (ROIs) generated by activated macrophages pre-treated with lipopolysaccharides (LPS), one of the major components of Salmonella outer membrane. We also showed that Salmonella attacks macrophages by a novel mechanism through the induction of apoptosis with large amounts of LPS and protein synthesis inhibition, in addition to the well-known mechanisms of type-three secretion system (TTSS)-induced cell damage, including InvA, an attacking, virulent factor of Salmonella. We showed that macrophages could escape from this type of cell death by LPS-induced macrophage activation and LPS-tolerance.
The combination of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin with rituximab (DA-EPOCH-R) is used for non-Hodgkin lymphoma patients. Febrile neutropenia (FN) is a common complication of treatment with myelo-suppressive chemotherapy, so preventing FN is important for maintaining chemotherapy dosage. Recently, pegfilgrastim has been used as the primary prophylaxis of FN in Japan, but there have been few cases reported using pegfilgrastim for the primary prophylaxis in DA-EPOCH-R. In this study, we retrospectively compared the efficacy of pegfilgrastim with that of filgrastim in patients receiving DA-EPOCH-R in Hiroshima University Hospital. Efficacy assessment was based on incidence of FN and serious neutropenia (neutrophil count <500/μL), hospitalization days and chemotherapy dosage level. Ten patients met the inclusion criteria: pegfilgrastim (n=5, 30 cycles) or filgrastim (n=5, 16 cycles). No difference in efficacy existed between pegfilgrastim and filgrastim in the first cycle; however, 2 of 5 patients in filgrastim group reduced dose level in the total cycles of chemotherapy, no patients in pegfilgrastim group reduced. In conclusion, pegfilgrastim seemed better than filgrastim for the primary prophylaxis in DA-EPOCH-R.
The combination of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin with rituximab (DA-EPOCH-R) is used for treatment of non-Hodgkin lymphoma. Febrile neutropenia (FN) is a common complication of treatment with myelo-suppressive chemotherapy, therefore, preventing FN is important for successful treatment. The authors compared the efficacy of pegfilgrastim with that of filgrastim in patients receiving DA-EPOCH-R and showed that pegfilgrastim seems to be better than filgrastim for the primary prophylaxis, maintaining chemotherapy dosage, and reducing hospital duration.
In this study, we propose a new technique for evaluating wetting and adhesion of lotions to skin using surface tension measurements, contact angle measurements and calculations based on the Owens-Wendt-Rabel-Kaelble (OWRK) method. Three prescription lotions (Napageln® Lotion 3%, Sumilu® Lotion 3% and Felbinac Lotion 3% ｢Rakool｣） and two over-the-counter lotions (Feitas® Lotion and Salomethyl® FB Lotion α) were used. Based on the dispersive and polar components of the surface free energy of Yucatan micro pig (YMP) skin, isograms of contact angle (wetting envelope) and adhesion work of the YMP skin surface were constructed. Plotting the surface tension and its polar component of lotions on this isogram revealed that it is possible to predict the wettability and adhesion of lotions to YMP skin. Such diagrams can be easily constructed even using the surface free energy of other types of skin, such as that of humans and hairless mice. This evaluation method may be applicable to other external use medicines.
We herein present the case of a 66-year-old Japanese man with Fanconi's syndrome. He had been receiving adefovir dipivoxil (ADV) for the treatment of entecavir (ETV)-resistant chronic hepatitis B (CHB) for four years in his 8-year treatment of hepatocellular carcinoma (HCC), but was referred to our hospital after increased levels of bone pain in his ribs, knees, and ankles. Renal dysfunction, hypophosphatemia, and increased levels of bone alkaline phosphatase were found by a hematology test after admission for treatment of HCC. Radiography and 99m Tc-labeled hydroxymethylene diphosphonate (HMDP) scintigraphy revealed multiple insufficiency fractures in the ribs, knees, ankles, and heels. After switching from ADV to tenofovir disoproxil fumarate (TDF) and treatment with calcitriol and sodium dihydrogenphosphate, the patient's serum phosphate levels slightly increased and renal dysfunction did not improve, but after six months his clinical symptoms disappeared. To detect and prevent adverse effects from ADV, physicians and pharmacists should carefully monitor renal function and serum phosphate levels in patients with hepatitis B virus (HBV) treated for a long time with ADV.
The effectiveness of steroid rotation from dexamethasone to prednisolone for hiccups caused by dexamethasone for antiemetic chemotherapy has been reported overseas, but has not been reported in Japan. The effectiveness of steroid rotation in Japanese individuals is unclear because ethnic differences and variations in glucocorticoid receptors affect sensitivity to dexamethasone. We report a case of the effectiveness of steroid rotation in a Japanese patient with hiccups caused by dexamethasone for antiemetic chemotherapy. A 74-year-old man was diagnosed as having stage IV gastric cancer. Chemotherapy was initiated using S-1 (80 mg/d on Days 1-21) and cisplatin (80 mg on Day 8), with dexamethasone (8 mg/d on Day 8 intravenously and on Days 9-11 orally) as antiemetic. Severe hiccups developed on Day 10 and resolved on Day 11 by the 1st cycle of chemotherapy. Subcutaneous injection of atropine by the 5th cycle and ingestion of Syakuyakukanzouto (Glycyrrhiza extract) by the 6th cycle did not effectively relieve the hiccups. By the 7th cycle, the hiccups resolved after the dose of dexamethasone was decreased from 8 mg/d to 4 mg/d but recurred by the 8th cycle. We then changed to prednisolone 30 mg/d from dexamethasone 4 mg/d by the 9th cycle; the hiccups completely resolved thereafter. Steroid rotation from dexamethasone to prednisolone completely controlled the hiccups, with no further recurrence. No emetic episodes occurred during chemotherapy. Therefore, this demonstrates the effectiveness of steroid rotation in a Japanese patient with hiccups caused by dexamethasone for antiemetic chemotherapy.