Search

The performance of the high temperature superconductor (HTS) is progressing rapidly and the enhancement in [J.sub.c] in Bi2223 long wires are achieved. The design study of the magnet by using the latest Dynamically Innovative bismuth-based HTS wire (DI-BSCCO) has shown that the higher magnetic field is produced with almost the same size of the magnet.

The progress on the development of high temperature superconducting magnets using Bi-2223 Ag-sheathed wire is reported. Two types of refrigerator cooled high temperature superconducting magnets, namely, a high magnetic field type and a large bore type, were successfully constructed. The magnets were developed using Bi-2223 silver-sheathed tape wire. Results show that one of the most important benefits of the magnets is their capability of rapid excitation.

Sumitomo Electric, DuPont and Aquafine successfully employed a high temperature superconducting (HTS) magnet system in separating mineral contaminants from kaolin clay. The magnetic separation effort involved the extraction of paramagnetic and ferromagnetic contaminants from five types of kaolin. Results from brightness tests reveal that conventional and HTS magnets generate consistent brightness at 2.0 T.

The powder-in-tube technique was utilized in fabricating silver-sheathed BiPbSrCaCuO 223 superconducting long length wires with a high critical current density of 10(super 4) A/cm2. Considerations involving crystal alignment and connectivity between grains and flux pinning were found to be useful in achieving higher critical current densities. High strength and high amperage wires were also also developed for applications in large scale magnets.

Anginosus group streptococci (AGS) are opportunistic pathogens that reside in the human oral cavity. The β-hemolytic strains of Streptococcus anginosus subsp. anginosus (SAA) produce streptolysin S (SLS), a streptococcal peptide hemolysin. In recent clinical scenarios, AGS, including this species, have frequently been isolated from infections and disorders beyond those in the oral cavity. Consequently, investigating this situation will reveal the potential pathogenicity of AGS to ectopic infections in humans. However, the precise mechanism underlying the cellular response induced by secreted SLS and its relevance to the pathogenicity of AGS strains remain largely unknown. This study aims to elucidate the mechanism underlying the host cellular response of the human acute monocytic leukemia cell line THP-1 to secreted SLS. In THP-1 cells incubated with the culture supernatant of β-hemolytic SAA containing SLS as the sole cytotoxic factor, increased Ca 2+ influx and elevated expression of proinflammatory cytokines were observed. Significantly reduced expression of SLS-dependent upregulated cytokine genes under Ca 2+ -chelating conditions suggests that Ca 2+ influx triggers SLS-dependent cellular responses. Furthermore, SLS-dependent enhanced expression of IL-8 was also implicated in the activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. The findings presented in this study are crucial for a comprehensive understanding of the real pathogenicity of SLS-producing β-hemolytic AGS in the latest clinical situations., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Atsushi Tabata reports financial support was provided by Japan Society for the Promotion of Science. Kazuto Ohkura reports financial support was provided by Japan Society for the Promotion of Science. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2024 The Authors.)

Neuroevolution is a promising approach for designing artificial neural networks using an evolutionary algorithm. Unlike recent trending methods that rely on gradient-based algorithms, neuroevolution can simultaneously evolve the topology and weights of neural networks. In neuroevolution with topological evolution, handling crossover is challenging because of the competing conventions problem. Mutation-based evolving artificial neural network is an alternative topology and weights neuroevolution approach that omits crossover and uses only mutations for genetic variation. This study enhances the performance of mutation-based evolving artificial neural network in two ways. First, the mutation step size controlling the magnitude of the parameter perturbation is automatically adjusted by a self-adaptive mutation mechanism, enabling a balance between exploration and exploitation during the evolution process. Second, the structural mutation probabilities are automatically adjusted depending on the network size, preventing excessive expansion of the topology. The proposed methods are compared with conventional neuroevolution algorithms using locomotion tasks provided in the OpenAI Gym benchmarks. The results demonstrate that the proposed methods with the self-adaptive mutation mechanism can achieve better performance. In addition, the adjustment of structural mutation probabilities can mitigate topological bloat while maintaining performance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hiraga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anginosus group streptococci (AGS) are opportunistic human pathogens of the oral cavity. The β-hemolytic subgroup of Streptococcus anginosus subsp. anginosus secretes streptolysin S (SLS) and exhibits not only hemolytic activity but also cytotoxicity toward cultured human cell lines. However, the detailed mechanism of action of SLS and the cellular responses of host cells have not yet been fully clarified. To determine the pathogenic potential of SLS-producing β-hemolytic S. anginosus subsp. anginosus, the SLS-dependent response induced in the human oral squamous cell carcinoma HSC-2 cells was investigated to determine the pathogenic potential of SLS-producing β-hemolytic S. anginosus subsp. anginosus. This study revealed that the Ca 2+ influx and the expression of immediate early genes (IEGs) encoding transcription factors such as early growth responses (EGRs) and activator protein-1 (AP-1) were greatly increased in HSC-2 cells incubated with the culture supernatant of SLS-producing β-hemolytic S. anginosus subsp. anginosus. Moreover, this SLS-dependent increase in expression was significantly suppressed by Ca 2+ chelation, except for jun. These results suggest that SLS caused Ca 2+ influx into the cells following greatly enhanced expression of IEG-encoding transcription factors. The results of this study may help in understanding the pathogenicity of SLS-producing AGS., (© 2023. Springer Nature Limited.)

Background: Some strains of Streptococcus mitis exhibit β-hemolysis due to the β-hemolytic activity of cholesterol-dependent cytolysin (CDC). Recently, a gene encoding an atypical lectinolysin-related CDC was found in S. mitis strain Nm-76. However, the product of this gene remains uncharacterized. We aimed to characterize this atypical CDC and its molecular functions and contribution to the pathogenicity of S. mitis strain Nm-76., Methods: Phylogenetic analysis of the CDC gene was conducted based on the web-deposited information. The molecular characteristics of CDC were investigated using a gene-deletion mutant strain and recombinant proteins expressed in Escherichia coli ., Results: The gene encoding CDC found in Nm-76 and its homolog are distributed among many S. mitis strains. This CDC is phylogenetically different from other previously characterized CDCs, such as S. mitis -derived human platelet aggregation factor (Sm-hPAF)/lectinolysin and mitilysin. Because this CDC possesses an additional N-terminal domain, including a discoidin motif, it was termed discoidinolysin (DLY). In addition to the preferential lysis of human cells, DLY displayed N-terminal domain-dependent facilitation of human erythrocyte aggregation and intercellular associations between human cells., Conclusion: DLY functions as a hemolysin/cytolysin and erythrocyte aggregation/intercellular association molecule. This dual-function DLY could be an additional virulence factor in S. mitis ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background/aim: Efficient drug encapsulation and regulation of drug release are important factors for sustained drug release and application for release-controlled anti-cancer and anti-inflammatory drug delivery. In the present study, a direct evaluation system for drug-release from model carrier (e.g., alginate-gel beads) was examined using the mitochondrial oxygen consumption rate as an index., Materials and Methods: Alginate-gel beads were coated with the uncoupler SF6847 (SF beads) and used as a model microparticle-type drug. The real-time monitoring of SF6847 release from prepared alginate-gel beads was performed using the mitochondrial oxygen consumption rate. Release profiles of nonsteroidal anti-inflammatory drugs [NSAIDs, mefenamic acid (MEF) and diclofenac (DIC)] from alginate-gel beads as well as SF beads were investigated using the real time monitoring system., Results: SF6847 release from alginate-gel beads was clearly detected using the rat liver mitochondrial oxygen consumption rate. The release features of MEF and DIC from alginate-gel beads were defined by the present trial monitoring system, and these NSAIDs exhibited different release profiles., Conclusion: The present drug monitoring system detected released drugs, and the release profile reflected the molecular properties of the test drugs. This system may be applied to the design and development of precise sustained drug release systems (e.g., anti-cancer and anti-inflammatory drugs)., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Type B aortic dissection (TBAD) is a rare but catastrophic complication of endovascular aneurysm repair (EVAR). We report two cases of TBAD occurring in the perioperative period of EVAR. The intraoperative and postoperative courses were unremarkable. Routine postoperative computed tomography angiography (CTA) revealed TBAD. Conservative treatment was successful, and no adverse aortic events occurred. TBAD that occurs in the perioperative period is likely to be iatrogenic in origin, uncomplicated, and managed with medical therapy: its prognosis is better than when the condition develops in the midterm postoperative period., Competing Interests: Disclosure StatementThe authors declare no conflict of interest., (© 2021 The Editorial Committee of Annals of Vascular Diseases.)

Background: From the design and synthesis of enantiomers, we can expect to obtain two compounds with different pharmacokinetics and pharmacological activities at the same time, which is thought to lead to the development of efficient anticancer agents. Chiral-2-nitroimidazole TX-2036 derivatives exhibit stereo-configuration (R- and S-configuration)-dependent tyrosine kinase inhibitory activity, and the activity of the tyrosine kinase domain of EGF receptor (EGFR-tyk) is suppressed. In order to clarify the reason why the effects on EGFR-tyk activity differ depending on stereoisomers, we tried to analyze the interaction between each TX-2036 derivative and EGFR-tyk., Materials and Methods: The 2-nitroimidazole-based radiosensitizer TX-2036 series were synthesized and their molecular features were examined using protein kinase inhibition assay and molecular structural analysis., Results: R-configured TXs (TX-2043, -2030, and -2036) exhibited more potent protein kinase inhibitory activity than S-configured TXs (TX-2044, - 2031, and -2037), and the IC 50 value of TX-2036 was 1.8 μM., Conclusion: R-configured TXs interacted with Lys 721 and Thr 766 of EGFR-tyk. The combinations of amino acid residues targeted by the S-configured TXs were different from each other (Ile 765 and Thr 766 (TX-2044), Ser 696 , Thr 766 , and Thr 830 (TX-2031), Gly 772 , Cys 773 , and Thr 830 (TX-2037)). Preparing a series of isomers with different target sites was considered beneficial when the target was mutated., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The stereo-configuration (R-, S-configuration) of chiral-2-nitroimidazole derivatives alters their radiosensitizing activity. This study aimed at examining the molecular features of these enantiomers by molecular simulation techniques., Materials and Methods: A series of 2-nitroimidazole-based radiosensitizer TX-2036 molecules were synthesized, and their profiles were examined using molecular structural analysis such as conformation analysis, molecular orbital analysis, and electrostatic potential analysis., Results: R-configured TXs (TX-2043, -2030, -2036) had a weaker radiosensitizing activity than S-configured TXs (TX-2044, -2031, -2037), and R-compounds had a small minus electrostatic potential (ESP) field in the cyclopentene-1,3-dione region. S-configured TX-2046 had weaker radiosensitizing activity than R-configured TX-2045, and TX-2046 had a small minus ESP field as well as R-configured TX-2043, -2030, - 2036., Conclusion: The cyclopentene-1,3-dione involved in the small minus ESP field affected the radiosensitizing activity of the TX-2036 series of molecules., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Streptococcus anginosus subsp. anginosus (SAA) is one of the opportunistic pathogens in humans that inhabits the oral cavity. The type strain of SAA, NCTC10713 T , showed clear β-hemolysis on blood agar plates, and the sole β-hemolytic factor revealed two streptolysin S (SLS) molecules. SLS is well known as the peptide hemolysin produced from the human pathogen S. pyogenes and shows not only hemolytic activity on erythrocytes but also cytotoxic activity in cell culture lines in vitro and in vivo , such as in a mouse infection model. However, no cytotoxic activity of SLS produced from β-hemolytic SAA (β-SAA) has been reported so far. Objective and Design: In this study, the SLS-dependent cytotoxicity of the β-SAA strains including the genetically modified strains was investigated in vitro . Results: The SLS-producing β-SAA showed cytotoxicity in human cell culture lines under the co-cultivation condition and it was found that this cytotoxicity was caused by the SLS secreted into the extracellular milieu. Conclusion: The results from this study suggest that the SLS produced from β-SAA might indicate the cytotoxic potential similar to that of the SLS from S. pyogenes and the SLS-producing β-SAA would be recognized as "a wolf in sheep's clothing" More attention will be paid to the pathogenicity of β-hemolytic Anginosus group streptococci.

Background/aim: Sugar molecules are often used as a tool to structurally modify chemical compounds. The features of synthesized sugar-conjugated TX-1877 derivatives were herein examined., Materials and Methods: The molecular stabilities (reactivity) and hydrophobicities of sugar (e.g., monosaccharide and tetra-O-acetylated monosaccharide)-conjugated TXs were analyzed using a molecular simulation (e.g. molecular mechanics (MM) and molecular orbital (MO) analysis)., Results: The hydrophobicities of TX-1877 derivatives were increased by tetra-O-acetylation, and TX-2244 exhibited the most potent radiosensitizing activity (enhancement ratio: ER=2.30)., Conclusion: The conformations and hydrophobicities of chemical compounds may be controlled by adding monosaccharide- and tetra-O-acetyl-conjugated sugars to TX-1877., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: To prevent haemodynamic stroke during cardiovascular surgery in patients with carotid stenosis, we routinely evaluated magnetic resonance angiography and selectively evaluated brain perfusion single-photon emission computed tomography with acetazolamide challenge. Off-pump surgery was preferred when cerebral blood flow reserve was impaired. This strategy's usefulness was investigated., Methods: Among the 1059 consecutive patients who underwent preoperative carotid screening by magnetic resonance angiography, 84 (7.9%) patients had >50% stenosis; 45 of them underwent brain single-photon emission computed tomography. The severity of cerebral blood flow compromise was estimated by the proportion of Stage 2 area in the affected territory, in which both resting blood flow (<32 ml/min) and flow reserve (<10%) were reduced., Results: Perioperative stroke occurred in 1.7% overall (18/1059), in 6% (5/84) of those with carotid stenosis and in 1.3% (13/975) of those without stenosis (P = 0.010). On subgroup analysis, carotid stenosis was associated with an increased risk of stroke in the on-pump surgery group [n = 949, 5/59 (9%) with stenosis vs 11/890 (1.1%) without stenosis, P = 0.002], while it was not in the off-pump group [n = 110, 0/25 (0%) with stenosis vs 2/85 (2%) without stenosis, P = 0.59]. With respect to the role of acetazolamide single-photon emission computed tomography, 2 of the 4 patients with Stage 2 area >10% undergoing on-pump surgery without preceding carotid revascularization developed stroke, while none of the 21 patients with Stage 2 area <10% undergoing on-pump surgery developed stroke (P = 0.020)., Conclusions: Carotid stenosis is a risk factor for perioperative stroke in on-pump surgery. Patients with large Stage 2 area (>10%) are at increased risk of perioperative stroke when on-pump surgery is performed.

Aim: We previously reported that stroke-prone spontaneously hypertensive rat/Ezo (SHRSP/Ezo) has high validity as an attention deficit/hyperactivity disorder (AD/HD) animal model, based on its behavioral phenotypes, such as inattention, hyperactivity, and impulsivity. Fronto-cortical dysfunction is implicated in the pathogenesis of AD/HD. In this study, we investigated prefrontal cortex (PFC) function in SHRSP/Ezo rats by electrophysiological methods and radioreceptor assay., Methods: We recorded excitatory postsynaptic potential in layer V pyramidal neurons in the PFC by intracellular recording method to assess synaptic plasticity in the form of long-term potentiation (LTP). We also performed N-methyl-d-aspartate acid (NMDA) receptor binding assay in the PFC and hippocampus using radiolabeled NMDA receptor antagonist [ 3 H]MK-801., Results: Theta-burst stimulation induced LTP in the PFC of genetic control, WKY/Ezo, whereas failed to induce LTP in that of SHRSP/Ezo. The K d value of [ 3 H]MK-801 binding for NMDA receptors in the PFC of SHRSP/Ezo was higher than in the WKY/Ezo. Neither the B max nor K d of [ 3 H]MK-801 binding in the SHRSP/Ezo hippocampus was significantly different to WKY/Ezo., Conclusion: These results suggest that the AD/HD animal model SHRSP/Ezo has NMDA receptor dysfunction in the PFC., (© 2018 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and pain. In the present study, we examined the effects of celecoxib, a cyclooxygenase-2 (COX-2)-selective NSAID, on rat liver mitochondrial function. Celecoxib dose-dependently induced mitochondria swelling, which was not suppressed by cyclosporine A (CsA). The oxygen consumption rate in mitochondria-suspended solution was facilitated by the addition of celecoxib, and its uncoupling activity was observed. Celecoxib also suppressed SF6847-induced uncoupling, and appeared to exert inhibitory effects on the electron transport chain. Celecoxib suppressed the state 3 oxygen consumption rate in the presence of ADP. Protein release from the mitochondrial matrix was detected following the addition of celecoxib, and aldehyde dehydrogenase 2 (ALDH2) and hydroxymethylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2) bands were confirmed in a Western blot analysis. On the other hand, protein release of cytochrome C (CytC), which is an inducer of apoptosis, from the intermembrane space was not observed. Celecoxib enhanced the membrane permeability of human erythrocytes and synthesized liposomes dose-dependently. It then induced the membrane-involving mitochondrial swelling and suppressed mitochondrial function.

Background: To date, two cyclo-oxygenase (COX) isoforms, COX1 and COX2, have been identified. In the present study, the COX-inhibitory activities of TX-1123 derivatives with the 2-hydroxyarylidene-4-cyclopentene-1,3-dione structure were examined, and the binding profiles of TX-1123 to COXs were analyzed using docking simulations., Materials and Methods: X-Ray data on COX1 [protein data bank (PDB) ID=1PGG] and COX2 (PDB ID=3LN1) were used for molecular interactive simulations. The interactive profiles of TX-1123 derivatives with COXs were examined using a molecular simulation technique with Molegro Virtual Docker (CLC bio, Aarhus, Denmark)., Results: TX-1123 exhibited COX1-inhibitory activity [half-maximal-inhibitory concentration (IC 50 )=1.57×10 -5 M]. The COX2 inhibitory activity of TX-1123 was potent (IC 50 =1.16×10 -6 M), and the ratio of COX1/COX2 inhibition was 13.5. TX-1123 bound to the COX2 molecule, and the oxygen atom of the 4-cyclopentene-1,3-dione region of TX-1123 interacted with Cys 26 and Gln 447 of COX2., Conclusion: The TX-1123-binding pocket of COX2 differs from that of the COX2-selective celecoxib-binding pocket. TX-1123 exhibited a different COX2-interactive mechanism from that of celecoxib., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Unlabelled: Recently, companion diagnostics with nuclear medicine techniques have been anticipated as more suitable means than biopsy for predicting treatment efficacy. The anticancer effect of capecitabine, an orally administered chemotherapeutic agent activated by thymidine phosphorylase (TP), is positively associated with tumor TP expression levels. This study aimed to assess whether TP imaging using a radiolabeled uracil derivative, (123)I-5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ((123)I-IIMU), could predict the efficacy of capecitabine treatment., Methods: Sensitivity to doxifluridine, a metabolite of capecitabine and direct substrate for TP, was assessed by water-soluble tetrazolium salt assays in vitro for 3 human colon cancer cell lines with different TP expression profiles. The intracellular uptake and retention of (123)I-IIMU were evaluated. Mice inoculated with each cell line were treated with capecitabine for 2 wk, and tumor growth was compared. In vivo distribution studies and SPECT/CT imaging of (123)I-IIMU were performed in inoculated mice., Results: In vitro experiments showed a positive relation between TP expression levels and doxifluridine sensitivity. In vitro studies revealed that intracellular uptake and retention of (123)I-IIMU were dependent on TP expression levels. In vivo experiments in inoculated mice showed that (123)I-IIMU accumulation in tumor tissue was in line with TP expression levels and susceptibility to capecitabine treatment. Moreover, SPECT/CT imaging of (123)I-IIMU in tumor-inoculated mice showed that (123)I-IIMU reflects TP expression levels in tumor tissues., Conclusion: (123)I-IIMU could be used as an in vivo companion diagnostic for predicting the efficacy of capecitabine treatment., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Protein tyrosine kinases (PTKs) play major roles in signal transduction during cell proliferation and apoptosis. Tyrphostin AG17 was previously shown to be a potent tumor growth inhibitor, while AG17 induced apoptosis and inhibited activity of cyclin-dependent kinase 2. We herein describe the binding features of tyrphostin AG17 analogs, such as TX-1123, with Src kinase (Src-K)., Materials and Methods: Structural data for Src-K were obtained from a protein data bank (ID=2SRC), and the molecular interactions between Src-K and TX-1123 derivatives were examined., Results: TX-1123 exihibited potent Src-K inhibitory activity (half maximal-inhibitory concentration=2.2 μM), and fit into the pocket of the Src-K molecule as well as c-AMP did., Conclusion: The binding profiles of TX-1123 derivatives differed from each other, while their Src-K inhibitory activities were affected by their fit in the Src-K molecule., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objectives: We have previously reported that transesophageal motor evoked potential is feasible and more stable than transcranial motor evoked potential. This study aimed to investigate the efficacy of transesophageal motor evoked potential to monitor spinal cord ischemia., Methods: Transesophageal and transcranial motor evoked potentials were recorded in 13 anesthetized dogs at the bilateral forelimbs, anal sphincters, and hindlimbs. Spinal cord ischemia was induced by aortic balloon occlusion at the 8th to 10th thoracic vertebra level. In the 12 animals with motor evoked potential disappearance, occlusion was maintained for 10 minutes (n = 6) or 40 minutes (n = 6) after motor evoked potential disappearance. Neurologic function was evaluated by Tarlov score at 24 and 48 hours postoperatively., Results: Time to disappearance of bilateral motor evoked potentials was quicker in transesophageal motor evoked potentials than in transcranial motor evoked potentials at anal sphincters (6.9 ± 3.1 minutes vs 8.3 ± 3.4 minutes, P = .02) and hindlimbs (5.7 ± 1.9 minutes vs 7.1 ± 2.7 minutes, P = .008). Hindlimb function was normal in all dogs in the 10-minute occlusion group, and motor evoked potentials recovery (>75% on both sides) after reperfusion was quicker in transesophageal motor evoked potentials than transcranial motor evoked potentials at hindlimbs (14.8 ± 5.6 minutes vs 24.7 ± 8.2 minutes, P = .001). At anal sphincters, transesophageal motor evoked potentials always reappeared (>25%), but transcranial motor evoked potentials did not in 3 of 6 dogs. In the 40-minute occlusion group, hindlimb motor evoked potentials did not reappear in 4 dogs with paraplegia. Among the 2 remaining dogs, 1 with paraparesis (Tarlov 3) showed delayed recovery (>75%) of hindlimb motor evoked potentials without reappearance of anal sphincter motor evoked potentials. In another dog with spastic paraplegia, transesophageal motor evoked potentials from the hindlimbs remained less than 20%, whereas transcranial motor evoked potentials showed recovery (>75%)., Conclusions: Transesophageal motor evoked potentials may be superior to transcranial motor evoked potentials in terms of quicker response to spinal cord ischemia and better prognostic value., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Hepatotoxicity is a known side effect of nonsteroidal anti-inflammatory drugs (NSAIDs). In the present study, the effects of N-phenylanthranilic acid (NPA) scaffold NSAIDs on rat liver mitochondria were examined. Mefenamic acid (MEF, 200 µM) induced mitochondrial swelling, which was inorganic phosphate (Pi)-dependent and suppressed by cyclosporin A (CsA, 2.5 µM), similar to calcium-induced swelling. Mitochondrial swelling was also observed following the addition of 200 µM flufenamic acid (FLU), meclofenamic acid (MCL), and tolfenamic acid (TOL). Less swelling was observed with the addition of 200 µM diclofenac (DIC) or NPA. Diphenylamine (DPA)-induced swelling occurred in a Pi-independent manner and was not sensitive to CsA. The mechanism by which DPA interacted with the mitochondrial inner membrane differed from those of the other NPA scaffold NSAIDs. The addition of 50 µM MEF, MCL, TOL, and FLU had uncoupling effects in mitochondrial inner membrane. These NSAIDs dose-dependently obstructed electron transport in the respiratory chain. NSAIDs are known to have various dynamic structures, and the solvation free energies (dGWs: an index of stereo-hydrophobicity) of the conformers obtained were determined using a molecular orbital analysis. The relationship between the dynamic structures and swelling induced by NPA scaffold NSAIDs was also examined.