Objective: : Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. Methods: : This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 μM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. Results: : A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 μM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 μM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. Conclusion : The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Background/Aims: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. Methods: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)–28– erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). Results: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. Conclusions Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Purpose: Multidisciplinary care has become a cornerstone of colorectal cancer management. To evaluate the clinical efficacy of a geriatric multidisciplinary oncology clinic (GMOC), we analyzed the surgical treatment decision-making process and outcomes. Methods: This retrospective single-center study reviewed the data of patients aged ≥65 years who participated in the GMOC at a tertiary referral hospital between 2015 and 2021. The clinical adherence rate, comprehensive geriatric assessment, and a multidimensional frailty score (MFS) were obtained. The groups that were recommended and not recommended for surgery were compared, analyzing the factors impacting the decision and 1-year survival outcomes. Furthermore, the postoperative complications of patients who underwent surgery were evaluated. Results: A total of 165 patients visited the GMOC, and 74 had colorectal cancer (mean age, 85.5 years [range, 81.2–89.0 years]). Among patients with systemic disease (n = 31), 7 were recommended for surgery, and 5 underwent surgery. Among patients with locoregional disease (n = 43), 18 were recommended for surgery, and 12 underwent surgery. Patients recommended and not recommended for surgery had significantly different activities of daily living (ADL) (P = 0.024), instrumental ADL (P = 0.001), Mini-Mental State Examination (P = 0.014), delirium risk (P = 0.039), and MFS (P = 0.001). There was no difference in the 1-year overall survival between the 2 groups (P = 0.980). Of the 17 patients who underwent surgery, the median (interquartile range) of operation time was 165.0 minutes (120.0–270.0 minutes); hospital stay, 7.0 days (6.0–8.0 days); and 3 patients had wound complications. Conclusion Proper counseling of patients through the GMOC could lead to appropriate management and favorable outcomes.

Background: Dietary supplements (DS) use is known to be common among cancer survivors. However, detailed information on the factors influencing DS use seems insufficient, including cancer-related and psychological factors. Methods: Study subjects were 1,852 Korean adult cancer survivors recruited from cancer survivor clinic of two university-affiliated hospitals. Data were collected retrospectively through review of medical records and self-administered questionnaires. Psychological factors were assessed using Hospital Anxiety and Depression Scale (HADS) and Fear of Cancer Recurrence Inventory-Short Form. Factors associated the DS use were evaluated by multiple logistic regression analysis after adjusting for covariates. Results: The prevalence of long-term DS use was 15.7% in overall (17.5% in female and 11.6% in male). Female survivors were 3.14 times (95% confidence interval [CI], 1.89–5.22) more likely to use DS than male. In male cancer survivors, ever-smoking and previous radiotherapy were positively associated with DS use. In females, breast cancer survivors were 0.32 times less likely to use DS compared with stomach cancer survivors, and survivors with family history of cancer were 1.39 times more likely to use DS than those without. After adjusting for sociodemographic, clinical, and lifestyle factors, survivors with anxiety (HADS ≥8) used DS 1.38 times (95% CI, 1.01–1.91) more frequently, compared with those without anxiety. Conclusion Diverse factors such as female sex, cancer treatment modality, smoking history, family history and anxiety status were associated with DS use in Korean cancer survivors. Targeted strategies with consideration of these factors are needed for counseling DS use for cancer survivors.

Background: Dietary supplements (DS) use is known to be common among cancer survivors. However, detailed information on the factors influencing DS use seems insufficient, including cancer-related and psychological factors. Methods: Study subjects were 1,852 Korean adult cancer survivors recruited from cancer survivor clinic of two university-affiliated hospitals. Data were collected retrospectively through review of medical records and self-administered questionnaires. Psychological factors were assessed using Hospital Anxiety and Depression Scale (HADS) and Fear of Cancer Recurrence Inventory-Short Form. Factors associated the DS use were evaluated by multiple logistic regression analysis after adjusting for covariates. Results: The prevalence of long-term DS use was 15.7% in overall (17.5% in female and 11.6% in male). Female survivors were 3.14 times (95% confidence interval [CI], 1.89–5.22) more likely to use DS than male. In male cancer survivors, ever-smoking and previous radiotherapy were positively associated with DS use. In females, breast cancer survivors were 0.32 times less likely to use DS compared with stomach cancer survivors, and survivors with family history of cancer were 1.39 times more likely to use DS than those without. After adjusting for sociodemographic, clinical, and lifestyle factors, survivors with anxiety (HADS ≥8) used DS 1.38 times (95% CI, 1.01–1.91) more frequently, compared with those without anxiety. Conclusion Diverse factors such as female sex, cancer treatment modality, smoking history, family history and anxiety status were associated with DS use in Korean cancer survivors. Targeted strategies with consideration of these factors are needed for counseling DS use for cancer survivors.

PURPOSE: Data on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC. MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL. RESULTS: Fifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015). CONCLUSION: Olanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV.
Antiemetics ; Dexamethasone ; Drug Therapy* ; Humans ; Nausea* ; Quality of Life ; Vomiting*

To evaluate the carcinogenicity of p27 knockout (KO) mice with RNA-guided endonuclease (RGENs)-mediated p27 mutant exon I gene (IΔ), alterations in the carcinogenic phenotypes including tumor spectrum, tumor suppressor proteins, apoptotic proteins and cell cycle regulators were observed in p27 (IΔ) KO mice after treatment with 7,12-Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)(DT) for 5 months. The target region (544~571 nt) in exon I of the p27 gene was successfully disrupted in p27 (IΔ) KO mice using the RGEN-induced non-homologous end joining (NHEJ) technique. After DT exposure for 5 months, a few solid tumors (identified as squamous cell carcinoma) developed on the surface of back skin of DT-treated p27 (IΔ) KO mice. Also, squamous cell hyperplasia with chronic inflammation was detected in the skin dermis of DT-treated p27 (IΔ) KO mice, while the Vehicle+p27 (IΔ) KO mice and WT mice maintained their normal histological skin structure. A significant increase was observed in the expression levels of tumor suppressor protein (p53), apoptotic proteins (Bax, Bcl-2 and Caspase-3) and cell-cycle regulator proteins (Cyclin D1, CDK2 and CDK4) in the skin of DT-treated p27 (IΔ) KO mice, although their enhancement ratio was varied. Taken together, the results of the present study suggest that squamous cell carcinoma and hyperplasia of skin tissue can be successfully developed in new p27 (IΔ) KO mice produced by RGEN-induced NHEJ technique following DT exposure for 5 months.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Carcinogenesis ; Carcinoma, Squamous Cell* ; Cell Cycle ; Dermis ; Epithelial Cells* ; Exons ; Hyperplasia* ; Inflammation ; Mice* ; Phenotype ; Skin ; Tumor Suppressor Proteins

Regulation of gastrointestinal hormones have been reported in animal models for constipation undergoing laxative therapy when administered herbal products. We undertook to investigate whether the laxative activity of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) affects the regulation of gastrointestinal hormones, by examining the concentration of four hormones and the activation of their receptors in the loperamide (Lop)-induced constipation model. Stool parameters, including number, weight and water content, were significantly recovered in the Lop+GEGR treated group, relative to the Lop+vehicle treated group; however, food intake and water consumption were maintained at a constant level. Also, a similar recovery was detected for thickness of mucosa, muscle and flat luminal surface in the Lop+GEGR treated group. Furthermore, concentration of the four gastrointestinal hormones evaluated, namely, cholecystokinin (CCK), gastrin (GAS), somatostatin (SS) and motilin (MTL), were lower in the Lop+vehicle treated group than the No treated group, but were remarkably enhanced in the Lop+GEGR treated group. Moreover, the downstream signaling pathway of MTL and SS receptors were recovered after GEGR administration. Results of the present study therefore indicate that the laxative effects of GEGR treatment may be tightly related with the regulation of gastrointestinal hormones in the Lop-induced constipation model.
Animals ; Cholecystokinin ; Constipation* ; Drinking ; Eating ; Gastrins ; Gastrointestinal Hormones* ; Loperamide ; Models, Animal ; Motilin ; Mucous Membrane ; Phenobarbital ; Rats* ; Somatostatin ; Water

Korl:ICR mice, established by the Korean National Institute of Food and Drug Safety Evaluation (NIFDS), are characterized based on their genetic variation, response to gastric injury, and response to constipation inducers. To compare the inhibitory responses of ICR stocks obtained from three different sources to the anticancer drug cisplatin (Cis), alterations in tumor volume, histopathological structure, and toxicity were examined in Sarcoma 180 tumor-bearing Korl:ICR, A:ICR (USA source), and B:ICR (Japan source) mice treated with low and high concentrations of Cis (L-Cis and H-Cis, respectively). Tumor size and volume were lower in H-Cis-treated mice than in L-Cis-treated mice in all three ICR stocks with no significant differences among stocks. There was a significant enhancement of the necrotizing areas in the histological structures in the L-Cis- and H-Cis-treated groups relative to that in the untreated group. The necrotizing area changes were similar in the Sarcoma 180 tumor-bearing Korl:ICR, A:ICR, and B:ICR mice. However, there were stock-bases differences in the serum biomarkers for liver and kidney toxic effects. In particular, the levels of AST, ALT and BUN increased differently in the three H-Cis-treated ICR stocks, whereas the levels of ALP and CRE were constant. Taken together, the results of the present study indicate that Korl:ICR, A:ICR, and B:ICR mice have similar overall inhibitory responses following Cis treatment of Sarcoma 180-derived solid tumors, although there were some differences in the magnitude of the toxic effects in the three ICR stocks.
Animals ; Biomarkers ; Cisplatin ; Constipation ; Genetic Variation ; Kidney ; Liver ; Mice ; Mice, Inbred ICR* ; Sarcoma ; Sarcoma 180 ; Tumor Burden