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Nanomedicines comprise multiple components, and particle density is considered an important property that regulates the biodistribution of administered nanomedicines. The density of nanoparticles is characterized by centrifugal methods, such as analytical ultracentrifugation. Particle size and distribution are key physicochemical and quality attributes of nanomedicines. In this study, we developed a novel profiling method applicable to liposomes and lipid nanoparticles (LNPs), based on particle size and density, using centrifugal field-flow fractionation (CF3). We evaluated the elution profiles of PEGylated liposomes of different sizes with various doxorubicin (DOX)-loading amounts using CF3. This method was applied to evaluate the drug release of DOX-loaded liposomes, intra- and inter-batch variability, reconstitution reproducibility of AmBisome®, and elution characteristics of LNPs in COVID-19 vaccines (Comirnaty® and SpikevaxTM). The data obtained in the present study underscore the significance of the proposed methodology and highlight the importance of profiling and characterizing liposomes and LNPs using CF3 fractograms and a multi-angle light-scattering detector.
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Phase-change materials such as Ge-Sb-Te (GST) exhibiting amorphous and crystalline phases can be used for phase-change random-access memory (PCRAM). GST-based PCRAM has been applied as a storage-class memory; however, its relatively low ON/OFF ratio and the large Joule heating energy required for the RESET process (amorphization) significantly limit the storage density. This study proposes a phase-change nitride, CrN, with a much wider programming window (ON/OFF ratio more than 105) and lower RESET energy (one order of magnitude reduction from GST). High-resolution transmission electron microscopy revealed a phase-change from the low-resistance cubic CrN phase into the highly resistive hexagonal CrN2 phase induced by the Soret-effect. The proposed phase-change nitride could greatly expand the scope of conventional phase-change chalcogenides and offer a strategy for the next-generation of PCRAM, enabling a large ON/OFF ratio (â¼105), low switching energy (â¼100 pJ), and fast operation (â¼30 ns).
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Understanding the cutting processability of cellulose nanofibril (CNF) films by continuous wave laser is important for precise shape processing that closely follows the design pattern. In this study, laser cutting of films made of surface-carboxylated CNFs with various counterionic species was performed to explore the factors that control the cutting processability. The cut width and the thermally affected width are mainly controlled by the laser irradiation energy per unit length. The processed cross section is tapered and rises above the film thickness. NMR analysis suggests that the pyrolysates contain water-soluble cello-oligosaccharides, the molecular weight of which varies with the type of CNF film. We consequently demonstrated that the COOH-type CNF film is preferable to the COONa-type CNF film for reducing the coloration residue and for processing the film into a shape that best follows the designed processing pattern.
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Mitochondrial stress and dysfunction play important roles in many pathologies. However, how cells respond to mitochondrial stress is not fully understood. Here, we examined the translational response to electron transport chain (ETC) inhibition and arsenite induced mitochondrial stresses. Our analysis revealed that during mitochondrial stress, tRNA modifications (namely f5C, hm5C, queuosine and its derivatives, and mcm5U) dynamically change to fine tune codon decoding, usage, and optimality. These changes in codon optimality drive the translation of many pathways and gene sets, such as the ATF4 pathway and selenoproteins, involved in the cellular response to mitochondrial stress. We further examined several of these modifications using targeted approaches. ALKBH1 knockout (KO) abrogated f5C and hm5C levels and led to mitochondrial dysfunction, reduced proliferation, and impacted mRNA translation rates. Our analysis revealed that tRNA queuosine (tRNA-Q) is a master regulator of the mitochondrial stress response. KO of QTRT1 or QTRT2, the enzymes responsible for tRNA-Q synthesis, led to mitochondrial dysfunction, translational dysregulation, and metabolic alterations in mitochondria-related pathways, without altering cellular proliferation. In addition, our analysis revealed that tRNA-Q loss led to a domino effect on various tRNA modifications. Some of these changes could be explained by metabolic profiling. Our analysis also revealed that utilizing serum deprivation or alteration with Queuine supplementation to study tRNA-Q or stress response can introduce various confounding factors by altering many other tRNA modifications. In summary, our data show that tRNA modifications are master regulators of the mitochondrial stress response by driving changes in codon decoding.
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Dissolving microneedles (MNs) are novel transdermal drug delivery systems that can be painlessly self-administered. This study investigated the effects of experimental conditions on the mechanical characterization of dissolving MNs for quality evaluation. Micromolding was used to fabricate polyvinyl alcohol (PVA)-based dissolving MN patches with eight different cone-shaped geometries. Axial force mechanical characterization test conditions, in terms of compression speed and the number of compression needles per test, significantly affected the needle fracture force of dissolving MNs. Characterization using selected test conditions clearly showed differences in the needle fracture force of dissolving MNs prepared under various conditions. PVA-based MNs were divided into two groups that showed buckling and unbuckling deformation, which occurred at aspect ratios (needle height/base diameter) of 2.8 and 1.8, respectively. The needle fracture force of PVA-based MNs was negatively correlated with an increase in the needle's aspect ratio. Higher residual water or higher loading of lidocaine hydrochloride significantly decreased the needle fracture force. Therefore, setting appropriate methods and parameters for characterizing the mechanical properties of dissolving MNs should contribute to the development and supply of appropriate products.
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The purpose of this study was to demonstrate Japanese radiographic examination codes JJ1017 in establishing typical values for a wide variety of general radiography. About 200,000 sets of examination data were collected, including exposure conditions, JJ1017 code applied, examination room numbers and patient information. Typical values for adults, children, and infants were calculated from the collected data, and the following items were examined: comparing typical values of general radiography in Japan DRLs 2015 and typical values in a facility; comparison of typical values between X-ray equipment for examinations of DRLs 2015; comparison of typical values for different procedures at the same anatomical site; identification of examination items associated with high radiation doses. The total numbers of JJ1017 codes applicable to the examinations were 45,372 for adults, 542 for children, and 2339 for infants. To calculate the typical values and compare these with the DRLs, we used a combination of JJ1017 anatomical codes, posture codes, and direction of radiation codes. The combination of these codes allowed the calculation of a typical value and comparison with DRLs 2015. Comparison between devices reveals differences in radiation doses and provides an opportunity to review the characteristics of the devices and their operation to suggest dose reductions. By calculating typical values for examination items for which the DRLs were not available, we were able to identify examination items with high doses in a facility and suggest items that should be audited in the facility.
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Doses de Radiação , Criança , Adulto , Humanos , Japão , Radiografia , Raios X , Valores de ReferênciaRESUMO
Short-chain fatty acids (SCFAs) are produced by the intestinal microbiota during the fermentation of dietary fibers as secondary metabolites. Several recent studies reported that SCFAs modulate the development and function of immune-related cells. However, the molecular mechanisms by which SCFAs regulate mast cells (MCs) remain unclear. In the current study, we analyzed the function and gene expression of mouse MCs in the presence of SCFAs in vitro and in vivo. We found that the oral administration of valerate or butyrate ameliorated passive systemic anaphylaxis and passive cutaneous anaphylaxis in mice. The majority of SCFAs, particularly propionate, butyrate, valerate, and isovalerate, suppressed the IgE-mediated degranulation of bone marrow-derived MCs, which were eliminated by the Gi protein inhibitor pertussis toxin and by the knockdown of Gpr109a. A treatment with the HDAC inhibitor trichostatin A also suppressed IgE-mediated MC activation and reduced the surface expression level of FcεRI on MCs. Acetylsalicylic acid and indomethacin attenuated the suppressive effects of SCFAs on degranulation. The degranulation degree was significantly reduced by PGE2 but not by PGD2. Furthermore, SCFAs enhanced PGE2 release from stimulated MCs. The SCFA-mediated amelioration of anaphylaxis was exacerbated by COX inhibitors and an EP3 antagonist, but not by an EP4 antagonist. The administration of niacin, a ligand of GPR109A, alleviated the symptoms of passive cutaneous anaphylaxis, which was inhibited by cyclooxygenase inhibitors and the EP3 antagonist. We conclude that SCFAs suppress IgE-mediated activation of MCs in vivo and in vitro involving GPR109A, PGE2, and epigenetic regulation.
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Anafilaxia , Niacina , Camundongos , Animais , Anafilaxia/tratamento farmacológico , Anafilaxia/metabolismo , Niacina/farmacologia , Niacina/metabolismo , Dinoprostona/metabolismo , Butiratos/farmacologia , Butiratos/metabolismo , Valeratos/metabolismo , Mastócitos/metabolismo , Epigênese Genética , Imunoglobulina E/metabolismo , Degranulação CelularRESUMO
PURPOSE: We fabricated and characterized polyvinyl alcohol (PVA)-based dissolving microneedles (MNs) for transdermal drug delivery of apomorphine hydrochloride (APO), which is used in treating the wearing-off phenomenon observed in Parkinson's disease. METHODS: We fabricated MN arrays with 11 × 11 needles of four different lengths (300, 600, 900, and 1200 µm) by micromolding. The APO-loaded dissolving MNs were characterized in terms of their physicochemical and functional properties. We also compared the pharmacokinetic parameters after drug administration using MNs with those after subcutaneous injection by analyzing the blood concentration of APO in rats. RESULTS: PVA-based dissolving MNs longer than 600 µm could effectively puncture the stratum corneum of the rat skin with penetrability of approximately one-third of the needle length. Although APO is known to have chemical stability issues in aqueous solutions, the drug content in APO-loaded MNs was retained at 25°C for 12 weeks. The concentration of APO after the administration of APO-loaded 600-µm MNs that dissolved completely in skin within 60 min was 81%. The absorption of 200-µg APO delivered by MNs showed a Tmax of 20 min, Cmax of 76 ng/mL, and AUC0-120 min of 2,829 ngã»min/mL, compared with a Tmax of 5 min, Cmax of 126 ng/mL, and AUC0-120 min of 3,224 ngã»min/mL for subcutaneous injection. The bioavailability in terms of AUC0-120 min of APO delivered by MNs was 88%. CONCLUSION: APO-loaded dissolving MNs can deliver APO via skin into the systemic circulation with rapid absorption and high bioavailability.
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Apomorfina , Doença de Parkinson , Ratos , Animais , Apomorfina/farmacologia , Sistemas de Liberação de Medicamentos , Doença de Parkinson/tratamento farmacológico , Administração Cutânea , PeleRESUMO
PURPOSE: Resilience engineering is the ability of a system to adjust its own functions and maintain the required behavior in the face of changes and disturbances, and resilience potential is a necessary requirement. We aimed to clarify the relationship between resilience potential and error prevention cases. METHOD: Based on the error cases reported in our department, we aggregated the relationship with resilience potential for each radiation treatment process. RESULT: As a result of tabulating the relationship, we were able to recognize and prevent errors by taking preventive measures from past cases. On the other hand, in cases that slipped through the check mechanism, errors were discovered because of a sense of discomfort in unusual situations, and some error cases could be prevented by increasing the resilience potential. CONCLUSION: This study found that preparation, observation, coping, and utilization of past experiences are related to resilience potential in preventive cases.
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Resiliência Psicológica , Capacidades de Enfrentamento , Inquéritos e QuestionáriosRESUMO
Recently, TNF receptor type 2 (TNFR2) signaling was found to be involved in the proliferation and activation of regulatory T cells (Tregs), a subpopulation of lymphocytes that suppress immune responses. Tregs mediate peripheral immune tolerance, and the disruption of their functions causes autoimmune diseases or allergy. Therefore, cell expanders or regulators of Tregs that control immunosuppressive activity can be used to treat these diseases. We focused on TNFR2, which is preferentially expressed on Tregs, and created tumor necrosis factor-α (TNF-α) muteins that selectively activate TNFR2 signaling in mice and humans, termed R2agoTNF and R2-7, respectively. In this study, we attempted to optimize the structure of muteins to enhance their TNFR2 agonistic activity and stability in vivo by IgG-Fc fusion following single-chain homo-trimerization. The fusion protein, scR2agoTNF-Fc, enhanced the expansion of CD4+CD25+ Tregs and CD4+Foxp3+ Tregs and contributed to their immunosuppressive activity ex vivo and in vivo in mice. The prophylactic administration of scR2agoTNF-Fc suppressed inflammation in contact hypersensitivity and arthritis mouse models. Furthermore, scR2-7-Fc preferentially expanded Tregs in human peripheral blood mononuclear cells via TNFR2. These TNFR2 agonist-Fc fusion proteins, which have bivalent structures, are novel Treg expanders.
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Artrite , Linfócitos T Reguladores , Animais , Humanos , Camundongos , Imunossupressores , Leucócitos Mononucleares , Receptores Tipo II do Fator de Necrose Tumoral/genética , Fator de Necrose Tumoral alfaRESUMO
The metabolic fate of pyrethroid insecticide cyphenothrin (1) [(RS)-α-cyano-3-phenoxybenzyl (1RS)-cis-trans-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate] in soils was investigated using 14C-labeled (1R)-cis/trans isomers at the cyclopropane ring. Both isomers degraded with half-lives of 19.0-47.4 days, and 48.9-56.0% and 27.5-38.7% of the applied radioactivity (AR) were mineralized to CO2 and incorporated into nonextractable residues (NER), respectively, after 120 days at 20 °C. NER analyses revealed 37.5-42.2% (cis-1) and 44.9-54.1% (trans-1) of each residue at 30/120 days were comprised of 14C-amino acids (AAs) as microbial products. Assuming that 50% of microbial biomass is AAs, it was estimated that 11.3-22.9%AR (cis-1, 75.0-84.4% of NER) and 13.9-30.4%AR (trans-1, 89.8-108.2% of NER) were nonhazardous biogenic NER (bio-NER), while type I/II xenobiotic NER (xeno-NER) characterized by silylation was insignificant at 0.9-1.0%/2.8-3.3%AR (cis-1). Detailed 14C-AA quantitation indicated a high relevance of the tricarboxylic acid cycle and pyruvate pathway during bio-NER formation, offering new insights into the microbial assimilation of the chrysanthemic moiety.
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Inseticidas , Piretrinas , Poluentes do Solo , Solo/química , Poluentes do Solo/metabolismo , Microbiologia do Solo , AminoácidosRESUMO
2D van der Waals (vdW) transition metal di-chalcogenides (TMDs) have garnered significant attention in the nonvolatile memory field for their tunable electrical properties, scalability, and potential for phase engineering. However, their complex switching mechanism and complicated fabrication methods pose challenges for mass production. Sputtering is a promising technique for large-area 2D vdW TMD fabrication, but the high melting point (typically Tm > 1000 °C) of TMDs requires elevated temperatures for good crystallinity. This study focuses on the low-Tm 2D vdW TM tetra-chalcogenides and identifies NbTe4 as a promising candidate with an ultra-low Tm of around 447 °C (onset temperature). As-grown NbTe4 forms an amorphous phase upon deposition that can be crystallized by annealing at temperatures above 272 °C. The simultaneous presence of a low Tm and a high crystallization temperature Tc can resolve important issues facing current phase-change memory compounds, such as high Reset energies and poor thermal stability of the amorphous phase. Therefore, NbTe4 holds great promise as a potential solution to these issues.
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Cholesterol crystals (CCs) in carotid plaques might be an indicator of vulnerability, although they have not been fully investigated and non-invasive methods of assessment have not been established. This study examines the validity of assessing CCs using dual-energy computed tomography (DECT) that uses X-rays with different tube voltages for imaging, allowing material discrimination. We retrospectively evaluated patients who had undergone preoperative cervical computed tomography angiography and carotid endarterectomy between December 2019 and July 2020. We developed CC-based material decomposition images (MDIs) by scanning CCs crystallized in the laboratory using DECT. We compared the percentage of CCs in stained slides defined by cholesterol clefts with the percentage of CCs displayed by CC-based MDIs. Thirty-seven pathological sections were obtained from 12 patients. Thirty-two sections had CCs; of these, 30 had CCs on CC-based MDIs. CC-based MDIs and pathological specimens showed a strong correlation. Thus, DECT allows the evaluation of CCs in carotid artery plaques.
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Estenose das Carótidas , Placa Aterosclerótica , Humanos , Estudos Retrospectivos , Artérias Carótidas/patologia , Placa Aterosclerótica/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Angiografia por Tomografia Computadorizada , ColesterolRESUMO
Government campaigns to replace off-patent brand pharmaceuticals with low cost generic products in national health insurance systems have apparently increased their production in the last two decades in Japan. The contamination of a batch of generic itraconazole tablets with the sleep inducer rilmazafone caused significant adverse events and related accidents in 2020, amidst increasing use of the generic products in healthcare. Investigations revealed many Good Manufacturing Practice (GMP) violations and other evidence of poor quality management in the manufacturing/marketing authorization holder (MAH). Urgent inspection of other MAHs found multiple cases of GMP noncompliance that resulted in temporary administrative suspension. Various quality issues, including nonconformity in stability monitoring, in these generic MAHs resulted in prolonged suspension of product shipments and shortages in medical institutions. These problems highlighted long-standing issues in quality management by MAHs and inspections by authorities, which had been neglected during rapid production expansion. This review introduces these manufacturing control and management problems and their countermeasures, and discusses the impact of habitual inadequate development processes that disregard the quality-by-design (QbD) perspective as the root cause of the issues.
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Contaminação de Medicamentos , Medicamentos Genéricos , Japão , Indústria FarmacêuticaRESUMO
In the present study, we evaluated the effects of kaempferol on bone marrow-derived mast cells (BMMCs). Kaempferol treatment significantly and dose-dependently inhibited IgE-induced degranulation, and cytokine production of BMMCs under the condition that cell viability was maintained. Kaempferol downregulated the surface expression levels of FcεRI on BMMCs, but the mRNA levels of FcεRIα, ß, and γ-chains were not changed by kaempferol treatment. Furthermore, the kaempferol-mediated downregulation of surface FcεRI on BMMCs was still observed when protein synthesis or protein transporter was inhibited. We also found that kaempferol inhibited both LPS- and IL-33-induced IL-6 production from BMMCs, without affecting the expression levels of their receptors, TLR4 and ST2. Although kaempferol treatment increased the protein amount of NF-E2-related factor 2 (NRF2)-a master transcription factor of antioxidant stress-in BMMCs, the inhibition of NRF2 did not alter the suppressive effect of kaempferol on degranulation. Finally, we found that kaempferol treatment increased the levels of mRNA and protein of a phosphatase SHIP1 in BMMCs. The kaempferol-induced upregulation of SHIP1 was also observed in peritoneal MCs. The knockdown of SHIP1 by siRNA significantly enhanced IgE-induced degranulation of BMMCs. A Western blotting analysis showed that IgE-induced phosphorylation of PLCγ was suppressed in kaempferol-treated BMMCs. These results indicate that kaempferol inhibited the IgE-induced activation of BMMCs by downregulating FcεRI and upregulating SHIP1, and the SHIP1 increase is involved in the suppression of various signaling-mediated stimulations of BMMCs, such as those associated with TLR4 and ST2.
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Mastócitos , Receptores de IgE , Degranulação Celular , Imunoglobulina E/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Quempferóis/farmacologia , Quempferóis/metabolismo , Mastócitos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Receptores de IgE/genética , Receptores de IgE/metabolismo , RNA Mensageiro/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Controlling the physical stability of noncrystalline active pharmaceutical ingredients remains a major challenge in the development of amorphous formulations such as amorphous solid-dispersion (ASD) formulations. To establish new evaluation and formulation strategies, the spatial distribution of the crystal phase in bulk amorphous nifedipine (NFD) was investigated as a model. The crystallization of amorphous NFD and the effect of a deliberately added impurity were investigated using powder X-ray diffraction (PXRD), differential scanning calorimetry and real-time in situ X-ray micro-computed tomography (X-ray CT). The stability data of amorphous samples, i.e., NFD and a mixture of NFD with an oxidative degradation product of NFD, impurity A (Imp A), at a weight ratio of 90:10, presented as percent amorphous remaining, suggests that Imp A accelerates the bulk crystal growth of NFD. Real-time in situ X-ray CT results showed surface-enhanced crystal growth and cavity formation in solid NFD samples. Moreover, the crystals were heterogeneous in density. These results suggest that Imp A affects the physical stability of the amorphous NFD. X-ray CT equipped with a heating unit can aid in-situ evaluation and assessment of physicochemical properties and physical stability of amorphous samples and formulations.
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Contaminação de Medicamentos , Estabilidade de Medicamentos , Nifedipino , Varredura Diferencial de Calorimetria , Cristalização/métodos , Nifedipino/análise , Nifedipino/química , Solubilidade , Difração de Raios X , Microtomografia por Raio-XRESUMO
Protein S deficiency causes spinal cord infarction in rare cases. We herein report the first case of severe cervicothoracic cord infarction in an adolescent with protein S deficiency. A 16-year-old boy presented with neck pain, four-limb paralysis, and numbness. Magnetic resonance imaging revealed spinal artery infarction in the C4 to Th4 area. Protein S antigen and activity were decreased. The patient was diagnosed with protein S deficiency-associated cervicothoracic cord infarction, which was treated with anticoagulation. Protein S deficiency should be considered as a potential cause of spinal cord infarction in young healthy patients and should be appropriately treated with anticoagulation.
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Ataque Isquêmico Transitório , Deficiência de Proteína S , Masculino , Humanos , Adolescente , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Deficiência de Proteína S/complicações , Deficiência de Proteína S/patologia , Infarto/complicações , Infarto/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , AnticoagulantesRESUMO
Mast cells (MCs) play key roles in IgE-mediated immunoresponses, including in the protection against parasitic infections and the onset and/or symptoms of allergic diseases. IgE-mediated activation induces MCs to release mediators, including histamine and leukotriene, as an early response, and to produce cytokines as a late phase response. Attempts have been made to identify novel antiallergic compounds from natural materials such as Chinese medicines and food ingredients. We herein screened approximately 60 compounds and identified salicylaldehyde, an aromatic aldehyde isolated from plant essential oils, as an inhibitor of the IgE-mediated activation of MCs. A degranulation assay, flow cytometric analyses, and enzyme-linked immunosorbent assays revealed that salicylaldehyde inhibited the IgE-mediated degranulation and cytokine expression of bone-marrow-derived MCs (BMMCs). The salicylaldehyde treatment reduced the surface expression level of FcεRI, the high affinity receptor for IgE, on BMMCs, and suppressed the IgE-induced phosphorylation of tyrosine residues in intercellular proteins, possibly Lyn, Syk, and Fyn, in BMMCs. We also examined the effects of salicylaldehyde in vivo using passive anaphylaxis mouse models and found that salicylaldehyde administration significantly enhanced the recovery of a reduced body temperature due to systemic anaphylaxis and markedly suppressed ear swelling, footpad swelling, and vascular permeability in cutaneous anaphylaxis.
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Anafilaxia , Mastócitos , Aldeídos/metabolismo , Anafilaxia/tratamento farmacológico , Anafilaxia/metabolismo , Animais , Degranulação Celular , Citocinas/metabolismo , Imunoglobulina E/metabolismo , Mastócitos/metabolismo , Camundongos , Receptores de IgE/metabolismo , Transdução de SinaisRESUMO
Particular batches of Moderna mRNA Coronavirus Disease 2019 (COVID-19) vaccine were recalled after foreign particles were found in some vaccine vials at the vaccination site in Japan in August 2021. We investigated the foreign particles at the request of the Ministry of Health, Labour and Welfare. Energy dispersive X-ray spectroscopy analysis suggested that the foreign particles found in the vials recalled from the vaccination sites were from stainless steel SUS 316L, which was in line with the findings of the root cause investigation by the manufacturer. The sizes of the observed particles ranged from <50 µm to 548 µm in the major axis. Similar foreign particles were also detected in 2 of the 5 vaccine vials of the same lot stored by the manufacturer, indicating that the foreign particles have already been administered to some people via vaccine. Observation of the vials of the same lot by digital microscope found smaller particles those were not detected by visual inspection, suggesting that more vials were affected. Contrarily, visual inspection and subvisible particulate matter test indicated no foreign particles in the vials of normal lots. Possible root cause and strategies to prevent such a deviation were discussed from technical and regulatory aspects.
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Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Japão/epidemiologia , Material ParticuladoRESUMO
The image management function of picture archiving and communication system (PACS) plays a very important role while electronically preserving medical records. However, details of these mechanisms vary from manufacturer to manufacturer, which could be a problem if system specifications or image management functions are not confirmed by a user during system installation or operation. The purpose of this research was to record the differences in PACS settings and image data management in hospitals. A questionnaire survey was conducted in 261 hospitals having the PACS system in Hokkaido prefecture, Japan. Questionnaire contents consisted of a face sheet and the following two items: 1) PACS image deletion method, 2) rules regarding the PACS receiving an image of data that was already registered. Results of the questionnaire survey showed that the image deletion method in the PACS server, and the overwriting rule in case of existent images being re-transmitted to the server were different between different hospitals. Furthermore, these variations were not dependent on the vendors or manufacturers, but on the settings of each hospital. Since the image management method of PACS is not standardized, we were considered to be needed more attention and appropriate regulation for safe management of electronic medical records as per the national guideline.