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A New Perspective on Dry Eye Classification: Proposal by the Asia Dry Eye Society

Tsubota K, Yokoi N, Watanabe H, Dogru M, Kojima T, Yamada M, et al.

Eye Contact Lens, 2020 Jan;46 Suppl 1:S2-S13.
PMID: 31425351 DOI: 10.1097/ICL.0000000000000643

The 2017 consensus report of the Asia Dry Eye Society (ADES) on the definition and diagnosis of dry eyes described dry eye disease as "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The report emphasized the instability of tear film and the importance of visual dysfunction in association with dry eyes, highlighting the importance of the evaluation of tear film stability. This report also discussed the concept of tear film-oriented therapy, which stemmed from the definition, and which is centered on provision of insufficient components in each tear film layer and ocular surface epithelium. The current ADES report proposes a simple classification of dry eyes based on the concept of tear film-oriented diagnosis and suggests that there are three types of dry eye: aqueous-deficient, decreased wettability, and increased evaporation. It is suggested that these three types respectively coincide with the problems of each layer: aqueous, membrane-associated mucins, and lipid/secretory mucin. Although each component cannot be quantitatively evaluated with the current technology, a practical diagnosis based on the patterns of fluorescein breakup is recommended. The Asia Dry Eye Society classification report suggests that for a practical use of the definition, diagnostic criteria and classification system should be integrated and be simple to use. The classification system proposed by ADES is a straightforward tool and simple to use, only through use of fluorescein, which is available even to non-dry eye specialists, and which is believed to contribute to an effective diagnosis and treatment of dry eyes.
Fulltext Albumin domain mutants with enhanced Aβ binding capacity identified by phage display analysis for application in various peripheral Aβ elimination approaches of Alzheimer's disease treatment

Ishima Y, Mimono A, Tuan Giam Chuang V, Fukuda T, Kusumoto K, Okuhira K, et al.

IUBMB Life, 2020 04;72(4):641-651.
PMID: 31794135 DOI: 10.1002/iub.2203

Deposition of amyloid protein, particularly Aβ1-42 , is a major contributor to the onset of Alzheimer's disease (AD). However, almost no deposition of Aβ in the peripheral tissues could be found. Human serum albumin (HSA), the most abundant protein in the blood, has been reported to inhibit amyloid formation through binding Aβ, which is believed to play an important role in the peripheral clearance of Aβ. We identified the Aβ binding site on HSA and developed HSA mutants with high binding capacities for Aβ using a phage display method. HSA fragment 187-385 (Domain II) was found to exhibit the highest binding capacity for Aβ compared with the other two HSA fragments. To elucidate the sequence that forms the binding site for Aβ on Domain II, a random screening of Domain II display phage biopanning was constructed. A number of mutants with higher Aβ binding capacities than the wild type were identified. These mutants exhibited stronger scavenging abilities than the wild type, as revealed via in vitro equilibrium dialysis of Aβ experiments. These findings provide useful basic data for developing a safer alternative therapy than Aβ vaccines and for application in plasma exchange as well as extracorporeal dialysis.
Attitudes of medical school deans toward interprofessional education in Western Pacific Region countries

Lee B, Celletti F, Makino T, Matsui H, Watanabe H

J Interprof Care, 2012 Nov;26(6):479-83.
PMID: 22830530 DOI: 10.3109/13561820.2012.706336

To examine the attitudes of medical school deans toward interprofessional education (IPE) and collaborative practice (CP), we conducted survey research in the Western Pacific Region. This regional survey was conducted as a collaborative research project with the World Health Organization. A survey was distributed to the medical school deans in Malaysia, the Philippines, Republic of Korea and Japan. Thirty-five surveys were returned from four countries. The survey demonstrated that many medical school deans have positive attitudes toward IPE and CP. However, respondents also reported that it is not easy to introduce interprofessional learning in their academic settings. It is suggested that collaboration between education systems and health systems is needed to introduce IPE in the academic setting. The possible role of international organizations is mentioned. This information helps to identify local efforts on which global health organizations and national governments can build.
Cell-penetrating mechanism of intracellular targeting albumin: Contribution of macropinocytosis induction and endosomal escape

Ichimizu S, Watanabe H, Maeda H, Hamasaki K, Ikegami K, Chuang VTG, et al.

J Control Release, 2019 06 28;304:156-163.
PMID: 31082432 DOI: 10.1016/j.jconrel.2019.05.015

We recently developed a cell-penetrating drug carrier composed of albumin (HSA) combined with palmitoyl-cyclic-(D-Arg)12. While it is possible that the palmitoyl-cyclic-(D-Arg)12/HSA enters the cell mainly via macropinocytosis, the mechanism responsible for the induction of macropinocytosis and endosomal escape remain unknown. We report herein that palmitoyl-cyclic-(D-Arg)12/HSA might interact with heparan sulfate proteoglycan and the chemokine receptor CXCR4 followed by multiple activations of the PKC/PI3K/JNK/mTOR signaling pathways to induce macropinocytosis. This result was further confirmed by a co-treatment with 70 kDa dextran, a macropinocytosis marker. Using liposomes that mimic endosomes, the leakage of 5,6-carboxyfluorescein from liposome was observed in the presence of palmitoyl-cyclic-(D-Arg)12/HSA only in the case of the anionic late endosome-like liposomes but not the neutral early endosome-like liposomes. Heparin largely inhibited this leakage, suggesting the importance of electrostatic interactions between palmitoyl-cyclic-(D-Arg)12/HSA and the late-endosomal membrane. Immunofluorescence staining and Western blotting data indicated that the intact HSA could be transferred from endosomes to the cytosol. These collective data suggest that the palmitoyl-cyclic-(D-Arg)12/HSA is internalized via macropinocytosis and intact HSA is released from the late endosomes to the cytoplasm before the endosomes fuse with lysosomes. Palmitoyl-cyclic-(D-Arg)12/HSA not only functions as an intracellular drug delivery carrier but also as an inducer of macropinocytosis.
Fulltext Changes in white matter fiber density and morphology across the adult lifespan: A cross-sectional fixel-based analysis

Choy SW, Bagarinao E, Watanabe H, Ho ETW, Maesawa S, Mori D, et al.

Hum Brain Mapp, 2020 08 15;41(12):3198-3211.
PMID: 32304267 DOI: 10.1002/hbm.25008

White matter (WM) fiber bundles change dynamically with age. These changes could be driven by alterations in axonal diameter, axonal density, and myelin content. In this study, we applied a novel fixel-based analysis (FBA) framework to examine these changes throughout the adult lifespan. Using diffusion-weighted images from a cohort of 293 healthy volunteers (89 males/204 females) from ages 21 to 86 years old, we performed FBA to analyze age-related changes in microscopic fiber density (FD) and macroscopic fiber morphology (fiber cross section [FC]). Our results showed significant and widespread age-related alterations in FD and FC across the whole brain. Interestingly, some fiber bundles such as the anterior thalamic radiation, corpus callosum, and superior longitudinal fasciculus only showed significant negative relationship with age in FD values, but not in FC. On the other hand, some segments of the cerebello-thalamo-cortical pathway only showed significant negative relationship with age in FC, but not in FD. Analysis at the tract-level also showed that major fiber tract groups predominantly distributed in the frontal lobe (cingulum, forceps minor) exhibited greater vulnerability to the aging process than the others. Differences in FC and the combined measure of FD and cross section values observed between sexes were mostly driven by differences in brain sizes although male participants tended to exhibit steeper negative linear relationship with age in FD as compared to female participants. Overall, these findings provide further insights into the structural changes the brain's WM undergoes due to the aging process.
Fulltext Characterization of Shigella sonnei in Malaysia, an increasingly prevalent etiologic agent of local shigellosis cases

Koh XP, Chiou CS, Ajam N, Watanabe H, Ahmad N, Thong KL

BMC Infect Dis, 2012;12:122.
PMID: 22606962 DOI: 10.1186/1471-2334-12-122

Shigellosis is a major public health concern worldwide, especially in developing countries. It is an acute intestinal infection caused by bacteria of the genus Shigella, with a minimum infective dose as low as 10-100 bacterial cells. Increasing prevalence of Shigella sonnei as the etiologic agent of shigellosis in Malaysia has been reported. As there is limited information on the genetic background of S. sonnei in Malaysia, this study aimed to characterize Malaysian S. sonnei and to evaluate the prospect of using multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) for subtyping of local S. sonnei.
Characterization of drug resistant Salmonella enterica serotype Typhimurium by antibiograms, plasmids, integrons, resistance genes and PFGE

Benacer D, Thong KL, Watanabe H, Puthucheary SD

J Microbiol Biotechnol, 2010 Jun;20(6):1042-52.
PMID: 20622506

Forty-seven Salmonella Typhimurium (33 zoonotic, 14 clinical) strains were tested for antimicrobial resistance using the standard disk diffusion method. Presence of relevant resistance genes and class 1 integrons were investigated by using PCR. Pulsed-field gel electrophoresis (PFGE) and plasmid profiling were carried out to determine the genomic diversity of Salmonella Typhimurium. Approximately 57.4% of S. Typhimurium were multidrug resistant (MDR) and showed high resistance rates to tetracycline (70.2%), sulphonamides (57.4%), streptomycin (53.1%), ampicillin (29.7%), nalidixic acid (27.6%), kanamycin (23.4%), chloramphenicol (21.2%) and trimethoprim (19.1%). Resistance towards cephalosporins was noted for cephalothin (27.6%), cephradine (21.2%), amoxicillin clavulanic acid (17.0%) and cephalexin (17.0%). Resistance genes, blaTEM, strA, aadA, sul1, sul2, tet(A), tet(B) and tet(C) were detected among the drug resistant strains. Thirty-three strains (70.2%) carried class 1 integrons, which were grouped in 9 different profiles. DNA sequencing identified sat, aadA, pse-1 and dfrA genes in variable regions on class 1 integrons. Thirty-five strains (74.4%) were subtyped to 22 different plasmid profiles, each with 1 - 6 plasmids (2.0 to 95 kb). PFGE subtyped the 47 strains into 39 profiles. In conclusion, high rates of multidrug-resistance were found among the Malaysian Salmonella Typhimurium strains. The emergence of multidrug-resistant Salmonella Typhimurium to cephalosporin antibiotics was also observed. The strains were very diverse and no persistent clone was observed. The emergence of MDR Salmonella Typhimurium is a worldwide problem and this report provides information for the better understanding of the prevalence and epidemiology of MDR S. Typhimurium in Malaysia.
Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery

Ichimizu S, Watanabe H, Maeda H, Hamasaki K, Nakamura Y, Chuang VTG, et al.

J Control Release, 2018 05 10;277:23-34.
PMID: 29530390 DOI: 10.1016/j.jconrel.2018.02.037

Human serum albumin (HSA) is a superior carrier for delivering extracellular drugs. However, the development of a cell-penetrating HSA remains a great challenge due to its low membrane permeability. We report herein on the design of a series of palmitoyl-poly-arginine peptides (CPPs) and an evaluation of their cell-penetrating effects after forming a complex with HSA for use in intracellular drug delivery. The palmitoyl CPPs forms a stable complex with HSA by anchoring itself to the high affinity palmitate binding sites of HSA. Among the CPPs evaluated, a cyclic polypeptide composed of D-dodecaarginines, palmitoyl-cyclic-(D-Arg)12 was the most effective for facilitating the cellular uptake of HSA by HeLa cells. Such a superior cell-penetrating capability is primarily mediated by macropinocytosis. The effect of the CPP on pharmacological activity was examined using three drugs loaded in HSA via three different methods: a) an HSA-paclitaxel complex, b) an HSA-doxorubicin covalent conjugate and c) an HSA-thioredoxin fusion protein. The results showed that cell-penetrating efficiency was increased with a corresponding and significant enhancement in pharmacological activity. In conclusion, palmitoyl-cyclic-(D-Arg)12/HSA is a versatile cell-penetrating drug delivery system with great potential for use as a nano-carrier for a wide diversity of pharmaceutical applications.
Fulltext Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions

Minayoshi Y, Maeda H, Yanagisawa H, Hamasaki K, Mizuta Y, Nishida K, et al.

Drug Deliv, 2018 Nov;25(1):1067-1077.
PMID: 29688069 DOI: 10.1080/10717544.2018.1464083

Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis. We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis. The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells. Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor. These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon. Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate. Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects. In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
Fulltext Distribution of Polysulfide in Human Biological Fluids and Their Association with Amylase and Sperm Activities

Ikeda M, Ishima Y, Chuang VTG, Sakai M, Osafune H, Ando H, et al.

Molecules, 2019 Apr 30;24(9).
PMID: 31052207 DOI: 10.3390/molecules24091689

Intracellular polysulfide could regulate the redox balance via its anti-oxidant activity. However, the existence of polysulfide in biological fluids still remains unknown. Recently, we developed a quantitative analytical method for polysulfide and discovered that polysulfide exists in plasma and responds to oxidative stress. In this study, we confirmed the presence of polysulfide in other biological fluids, such as semen and nasal discharge. The levels of polysulfide in these biological fluids from healthy volunteers (n = 9) with identical characteristics were compared. Additionally, the circadian rhythm of plasma polysulfide was also investigated. The polysulfide levels detected from nasal discharge and seminal fluid were approximately 400 and 600 μM, respectively. No correlation could be found between plasma polysulfide and the polysulfide levels of tear, saliva, and nasal discharge. On the other hand, seminal polysulfide was positively correlated with plasma polysulfide, and almost all polysulfide contained in semen was found in seminal fluid. Intriguingly, saliva and seminal polysulfide strongly correlated with salivary amylase and sperm activities, respectively. These results provide a foundation for scientific breakthroughs in various research areas like infertility and the digestive system process.
Epidemiology of internet behaviors and addiction among adolescents in six Asian countries

Mak KK, Lai CM, Watanabe H, Kim DI, Bahar N, Ramos M, et al.

Cyberpsychol Behav Soc Netw, 2014 Nov;17(11):720-8.
PMID: 25405785 DOI: 10.1089/cyber.2014.0139

Internet addiction has become a serious behavioral health problem in Asia. However, there are no up-to-date country comparisons. The Asian Adolescent Risk Behavior Survey (AARBS) screens and compares the prevalence of Internet behaviors and addiction in adolescents in six Asian countries. A total of 5,366 adolescents aged 12-18 years were recruited from six Asian countries: China, Hong Kong, Japan, South Korea, Malaysia, and the Philippines. Participants completed a structured questionnaire on their Internet use in the 2012-2013 school year. Internet addiction was assessed using the Internet Addiction Test (IAT) and the Revised Chen Internet Addiction Scale (CIAS-R). The variations in Internet behaviors and addiction across countries were examined. The overall prevalence of smartphone ownership is 62%, ranging from 41% in China to 84% in South Korea. Moreover, participation in online gaming ranges from 11% in China to 39% in Japan. Hong Kong has the highest number of adolescents reporting daily or above Internet use (68%). Internet addiction is highest in the Philippines, according to both the IAT (5%) and the CIAS-R (21%). Internet addictive behavior is common among adolescents in Asian countries. Problematic Internet use is prevalent and characterized by risky cyberbehaviors.
Erythrocyte Alloimmunity and Genetic Variance: Results from the Collaborative Study of Alloimmunity to Antigen Diversity in Asian Populations (All ADP)

Takeshita A, Watanabe H, Yamada C, Nadarajan VS, Permpikul P, Sinkitjasub A, et al.

Transfus Apher Sci, 2020 Oct;59(5):102944.
PMID: 33228922 DOI: 10.1016/j.transci.2020.102944

As an East-Asian international study, we evaluated erythrocyte alloimmunity by gender and history of transfusion or pregnancy. In total, data from more than 1,826,000 patients were analyzed, from whom 26,170 irregular erythrocyte antibodies were detected in 22,653 cases. Antibody frequencies in these cases were as follows: anti-E, 26.8%; anti-Lea, 20.0%; anti-P1, 7.1%; anti-M, 6.4%; anti-Mia, 5.6%; anti-c + E, 5.6%; anti-Leb, 4.6%; anti-D, 2.8%; anti-Fyb, 2.6%; anti-Lea+Leb, 2.5%; anti-Dia, 2.0%; and others. For pregnant patients, anti-D (12.7%) was statistically more frequent. For transfused patients, anti-E (37.3%), anti-c + E (9.5%), anti-C + e (3.3%) and anti-Jka (3.1%) were significantly more frequent.
Fiber-specific white matter analysis reflects upper motor neuron impairment in amyotrophic lateral sclerosis

Ogura A, Kawabata K, Watanabe H, Choy SW, Bagarinao E, Kato T, et al.

Eur J Neurol, 2022 Feb;29(2):432-440.
PMID: 34632672 DOI: 10.1111/ene.15136

BACKGROUND AND PURPOSE: To clarify the relationship between fiber-specific white matter changes in amyotrophic lateral sclerosis (ALS) and clinical signs of upper motor neuron (UMN) involvement, we performed a fixel-based analysis (FBA), a novel framework for diffusion-weighted imaging analysis.
METHODS: We enrolled 96 participants, including 48 nonfamilial ALS patients and 48 age- and sex-matched healthy controls (HCs), in this study and conducted whole-brain FBA and voxel-based morphometry analysis. We compared the fiber density (FD), fiber morphology (fiber cross-section [FC]), and a combined index of FD and FC (FDC) between the ALS and HC groups. We performed a tract-of-interest analysis to extract FD values across the significant regions in the whole-brain analysis. Then, we evaluated the associations between FD values and clinical variables.
RESULTS: The bilateral corticospinal tracts (CSTs) and the corpus callosum (CC) showed reduced FD and FDC in ALS patients compared with HCs (p
Fulltext Gluconobacter dominates the gut microbiome of the Asian palm civet Paradoxurus hermaphroditus that produces kopi luwak

Watanabe H, Ng CH, Limviphuvadh V, Suzuki S, Yamada T

PeerJ, 2020;8:e9579.
PMID: 32821539 DOI: 10.7717/peerj.9579

Coffee beans derived from feces of the civet cat are used to brew coffee known as kopi luwak (the Indonesian words for coffee and palm civet, respectively), which is one of the most expensive coffees in the world owing to its limited supply and strong market demand. Recent metabolomics studies have revealed that kopi luwak metabolites differ from metabolites found in other coffee beans. To produce kopi luwak, coffee beans are first eaten by civet cats. It has been proposed that fermentation inside the civet cat digestive tract may contribute to the distinctively smooth flavor of kopi luwak, but the biological basis has not been determined. Therefore, we characterized the microbiome of civet cat feces using 16S rRNA gene sequences to determine the bacterial taxa that may influence fermentation processes related to kopi luwak. Moreover, we compared this fecal microbiome with that of 14 other animals, revealing that Gluconobacter is a genus that is, uniquely found in feces of the civet cat. We also found that Gluconobacter species have a large number of cell motility genes, which may encode flagellar proteins allowing colonization of the civet gut. In addition, genes encoding enzymes involved in the metabolism of hydrogen sulfide and sulfur-containing amino acids were over-represented in Gluconobacter. These genes may contribute to the fermentation of coffee beans in the digestive tract of civet cats.
Isolation of an Escherichia coli O157:H7 strain producing Shiga toxin 1 but not Shiga toxin 2 from a patient with hemolytic uremic syndrome in Korea

Kim YB, Okuda J, Matsumoto C, Morigaki T, Asai N, Watanabe H, et al.

FEMS Microbiol Lett, 1998 Sep 01;166(1):43-8.
PMID: 9741083

Escherichia coli strains isolated from patients with diarrhea or hemolytic uremic syndrome (HUS) at Pusan University Hospital, South Korea, between 1990 and 1996 were examined for traits of the O157:H7 serogroup. One strain isolated from a patient with HUS belonged to the O157:H7 serotype, possessed a 60-MDa plasmid, the eae gene, and ability to produce Shiga toxin 1 but not Shiga toxin 2. Arbitrarily primed PCR analysis suggested that this strain is genetically very close to a O157:H7 strain isolated in Japan.
Measurement Invariance of the Internet Addiction Test Among Hong Kong, Japanese, and Malaysian Adolescents

Lai CM, Mak KK, Cheng C, Watanabe H, Nomachi S, Bahar N, et al.

Cyberpsychol Behav Soc Netw, 2015 Oct;18(10):609-17.
PMID: 26468915 DOI: 10.1089/cyber.2015.0069

There has been increased research examining the psychometric properties on the Internet Addiction Test (IAT) in different populations. This population-based study examined the psychometric properties and measurement invariance of the IAT in adolescents from three Asian countries. In the Asian Adolescent Risk Behavior Survey (AARBS), 2,535 secondary school students (55.9% girls) aged 12-18 years from Hong Kong (n=844), Japan (n=744), and Malaysia (n=947) completed a survey in 2012-2013 school year. A nested hierarchy of hypotheses concerning the IAT cross-country invariance was tested using multigroup confirmatory factor analyses. Replicating past findings in Hong Kong adolescents, the construct of the IAT is best represented by a second-order three-factor structure in Malaysian and Japanese adolescents. Configural, metric, scalar, and partial strict factorial invariance was established across the three samples. No cross-country differences on Internet addiction were detected at the latent mean level. This study provided empirical support for the IAT as a reliable and factorially stable instrument, and valid to be used across Asian adolescent populations.
Molecular characterization of Salmonella enterica serovar Typhimurium isolated from human, food, and animal sources in Malaysia

Ngoi ST, Lindstedt BA, Watanabe H, Thong KL

Jpn J Infect Dis, 2013;66(3):180-8.
PMID: 23698477

Salmonella Typhimurium is an important nontyphoidal Salmonella serovar associated with foodborne diseases in many parts of the world. This organism is the major causative agent of nontyphoidal salmonellosis in Malaysia. We aimed to investigate the genetic profiles of the strains isolated from clinical, zoonotic, and dietary sources in Malaysia using multilocus variable number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE). By focusing on the 5 common variable number tandem repeat (VNTR) loci, we found that PFGE (D = 0.99) was more discriminative than MLVA (D = 0.76). The low MLVA score might be because of a lack of VNTR loci STTR6 (81.0%) and STTR10pl (76.2%). Both subtyping methods suggested that our S. Typhimurium strains were largely endemic with limited genetic variation. Furthermore, we observed that biphasic S. Typhimurium strains were dominant (99%) and multidrug resistance was prevalent (50%) within our sample pool. The most frequently observed phenotypes were resistance to compound sulfonamides (49%), tetracycline (51%), and streptomycin (52%). In this study, we documented the genetic relationship, antimicrobial resistance characteristics, and flagellar-phase dominance among S. Typhimurium strains found in Malaysia.
Fulltext Neurological perspectives should be integrated into the management of tardive dyskinesia - expert opinion and proposed educational initiatives in Asia

Bhidayasiri R, Phokaewvarangkul O, Lim TT, Pal PK, Watanabe H, Cho JW, et al.

J Mov Disord, 2024 Apr 11.
PMID: 38600683 DOI: 10.14802/jmd.24068
Fulltext S-Nitrosated alpha-1-acid glycoprotein exhibits antibacterial activity against multidrug-resistant bacteria strains and synergistically enhances the effect of antibiotics

Ishima Y, Watanabe K, Chuang VTG, Takeda I, Kuroda T, Ogawa W, et al.

FASEB Bioadv, 2019 Mar;1(3):137-150.
PMID: 32123826 DOI: 10.1096/fba.1018

Alpha-1-acid glycoprotein (AGP) is a major acute-phase protein. Biosynthesis of AGP increases markedly during inflammation and infection, similar to nitric oxide (NO) biosynthesis. AGP variant A (AGP) contains a reduced cysteine (Cys149). Previously, we reported that S-nitrosated AGP (SNO-AGP) synthesized by reaction with a NO donor, possessed very strong broad-spectrum antimicrobial activity (IC50 = 10-9-10-6 M). In this study, using a cecal ligation and puncture animal model, we confirmed that AGP can be endogenously S-nitrosated during infection. Furthermore, we examined the antibacterial property of SNO-AGP against multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa to investigate the involvement of SNO-AGP in the host defense system. Our results showed that SNO-AGP could inhibit multidrug efflux pump, AcrAB-TolC, a major contributor to bacterial multidrug resistance. In addition, SNO-AGP decreased biofilm formation and ATP level in bacteria, indicating that SNO-AGP can revert drug resistance. It was also noteworthy that SNO-AGP showed synergistic effects with the existing antibiotics (oxacillin, imipenem, norfloxacin, erythromycin, and tetracycline). In conclusion, SNO-AGP participated in the host defense system and has potential as a novel agent for single or combination antimicrobial therapy.
Fulltext Tardive dyskinesia in Asia- current clinical practice and the role of neurologists in the care pathway

Bhidayasiri R, Phokaewvarangkul O, Shang HF, Lim TT, Cho JW, Pal PK, et al.

Front Neurol, 2024;15:1356761.
PMID: 38419696 DOI: 10.3389/fneur.2024.1356761

Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinical management of this challenging condition are scarce. However, neurologists have an essential role in managing the movement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally.

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