Teicoplanin is an important antibiotic for methicillin-resistant Staphylococcus aureus infections. To enhance its clinical effectiveness while preventing adverse effects, therapeutic drug monitoring (TDM) of teicoplanin trough concentration is recommended. Given the importance of the early attainment of therapeutic concentrations for treatment success, initial dosing regimens, including loading and maintenance doses, are deliberately designed based on patient information. However, initial dose planning for teicoplanin strongly relies on clinician expertise. This study aimed to use a machine learning (ML) approach to integrate clinicians’ knowledge into a predictive model for initial teicoplanin dose planning. First, we confirmed that dose planning by pharmacists specialized in TDM (TDM pharmacists) significantly improved early therapeutic target attainment for patients who were not admitted to intensive or high care units. Subsequently, we used a dataset of initial teicoplanin dose plans created by TDM pharmacists to train the model that emulates their dosing decision-making process. Although the prediction accuracies of the ML model were modest (45.8 and 66.7% for the loading and maintenance doses, respectively), the model successfully learned the basic policy of dose planning, suggesting that ML approaches have potential utility in supporting appropriate initial teicoplanin treatment.
Optimizing
the initial dosing of the glycopeptide antibiotic teicoplanin is crucial for
the effective treatment of methicillin-resistant Staphylococcus aureus
(MRSA) infections; however, it often relies on clinicians’ experience and
expertise. The authors first showed that pharmacists dedicated to antimicrobial
stewardship significantly improve early target teicoplanin exposure. Building
on this finding, they developed a machine-learning (ML) model to integrate pharmacists’
knowledge into initial dosing decisions. The resulting model reproduced
pharmacist dose-planning decisions, suggesting that ML-based approaches can
serve as complementary tools to ensure optimized initial therapy for MRSA.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by inflammation of the colon. Although various dextran sulfate sodium (DSS)-induced UC models are available, the traditional free-drinking model involves oral administration, which complicates the assessment of extracolonic organs because of widespread intestinal exposure. This study aimed to create a localized UC model through rectal administration of DSS and evaluate whether this approach minimized direct DSS exposure to the small intestine and liver. Rats received 40% DSS rectally for 13 d. Changes in body weight, Disease Activity Index, and histological scores were monitored. The effects of 5-aminosalicylic acid treatment were examined, and small intestinal morphology, inflammatory markers, bile flow, and mRNA levels of hepatic bile salt export pump were analyzed. Rectal DSS induced localized inflammation in the distal colon and rectum, mimicking key features of UC such as weight loss, mucosal injury, and elevated disease activity. Some of these effects were partially alleviated by 5-aminosalicylic acid treatment. The small intestine shortened without infiltration of inflammatory cells or cytokine increase, indicating a non-inflammatory structural change. Bile flow and hepatic bile salt export pump expression significantly decreased in DSS-treated rats, suggesting hepatobiliary excretory dysfunction. Overall, the rectal DSS model offers a controlled and reproducible way to induce colon-specific inflammation, overcoming the limitations of the free-drinking model, which hinders extracolonic evaluation due to oral DSS exposure. This model may provide a research basis for further study of inter-organ interactions, particularly gut–liver axis dysfunction and intestinal barrier-related drug absorption in UC.
[Highlighted Paper selected by Editor-in-Chief]
Ulcerative colitis (UC) is generally
considered a disease limited to the large intestine. However, UC may also
affect extra-colonic tissues. Conventional UC models induced by dextran sodium
sulfate (DSS) in drinking water may directly injure the small intestine. To
avoid this limitation, we established a novel UC model with localized rectal
inflammation. Despite no apparent small-intestinal inflammation, this model
showed small-intestinal shortening, villous atrophy, and altered bile-related
parameters. These findings suggest that localized colonic inflammation may
secondarily affect surrounding tissues beyond the large intestine, potentially
influencing nutrient and oral drug absorption.
Sotorasib is a molecularly targeted drug that exerts antitumor effects by selectively binding to KRAS G12C through a Michael addition reaction, irreversibly inhibiting KRAS. However, the frequent occurrence of adverse events, such as gastrointestinal and hepatic disorders, has raised major concerns. These toxicities are thought to arise from interactions between sotorasib and proteins other than KRAS in normal cells. In this study, we generated a specific antibody against sotorasib and established an immunohistochemical method capable of detecting sotorasib–protein conjugates. Using this technique, we clarified the localization of sotorasib–protein conjugates in the digestive tract of rats, including the duodenum, jejunum, ileum, and colon. Sotorasib–protein conjugates were strongly localized to the villous epithelial cells of the small intestine but were scarcely detected in the colon, highlighting regional differences. This study elucidates the localization of sotorasib–protein conjugates in the gastrointestinal tract of rats and provides important insights into the mechanisms underlying sotorasib-induced gastrointestinal disorders.
Gastrointestinal toxicity is a major
challenge in sotorasib therapy. In this study, the authors developed a
pioneering immunohistochemical approach using a sotorasib‑specific antibody to
visualize drug–protein conjugates in vivo.
Their cellular‑resolution mapping across the rat gastrointestinal tract
revealed marked accumulation in the villous epithelium of the small intestine,
in contrast to its minimal presence in the colon. These findings provide
critical mechanistic insights into sotorasib‑induced gastrointestinal toxicity
and establish a robust platform for evaluating on‑target and off‑target effects
of covalent KRAS G12C inhibitors.
Abortion remains a significant public health concern and often results from unintended pregnancies. Although abortion rates have declined, approximately 40% are still due to unplanned pregnancies. We conducted a subanalysis of the FIKA study, a survey on sexuality among Japanese women aged 18–45 years, to examine factors correlated with abortion. We analyzed responses obtained from 3228 sexually experienced women, who were categorized based on abortion history. Sources of knowledge about intercourse and contraceptives were assessed using a standardized questionnaire. A decision tree analysis was performed to identify associated risk factors. Among the participants, 410 women (12.7%) had undergone an abortion. Women who had undergone an abortion were significantly more likely to rely on friends as a source of contraceptive information than women who had not had an abortion (p = 0.0024). Participants with abortion experience showed greater variation in knowledge about contraceptive scores, with most of them being in the lowest knowledge group. Decision tree analysis revealed two key factors: sexual debut before the age of 17 years and only compulsory education. The abortion rate was 39.5% among women with both factors, compared to 7.9% among those with none. Early sexual initiation and limited education were strongly associated with abortion experience. Reliance on informal sources may also contribute to a poor understanding of reproductive health. These findings underscore the need for early, comprehensive, and formal sex education to improve sexual literacy and reduce unintended pregnancies.
Induced abortion is a major reproductive
health issue with important implications for education, access to information,
and women’s health. In this nationwide web-based questionnaire survey in Japan,
younger age at first sexual intercourse and lower educational attainment were
associated with a history of induced abortion among women aged 18–45 years. The
study also showed that women with abortion experience were more likely to rely
on informal information sources and had lower contraceptive knowledge. These
findings point to an urgent need for comprehensive, formal sexuality education
that reaches young people before they become sexually active.
Total Purine and Purine Base Content of Common Foodstuffs for Facilitating Nutritional Therapy for Gout and Hyperuricemia
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Kiyoko Kaneko, Yasuo Aoyagi, Tomoko Fukuuchi, Katsunori Inazawa, Noriko Yamaoka
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General Pharmacology of CKD-732, a New Anticancer Agent: Effects on Central Nervous, Cardiovascular, and Respiratory System
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Eun-Joo Kim, Won-Ho Shin
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Evaluation of Tumor Tissue Fixation Effects of Formulation Modified Mohs Pastes in Mice and Their Water-Absorbing Properties
Released on J-STAGE: December 01, 2018 | Volume 41 Issue 12 Pages 1824-1829
Maho Taguchi, Masato Shigeyama, Noriko Ogawa, Mikio Murata, Nobumitsu Hanioka, Hiromitsu Yamamoto, Hitomi Teramachi
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Association between Concomitant Use of Acyclovir or Valacyclovir with NSAIDs and an Increased Risk of Acute Kidney Injury: Data Mining of FDA Adverse Event Reporting System
Released on J-STAGE: February 01, 2018 | Volume 41 Issue 2 Pages 158-162
Zhihua Yue, Jinhai Shi, Haona Li, Huiyi Li
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Nephropathy II Decoction Attenuates Renal Fibrosis via Regulating TLR4 and Gut Microbiota Along the Gut-Kidney Axis
Released on J-STAGE: May 10, 2025 | Volume 48 Issue 5 Pages 577-594
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