• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.427-438
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• 2022

Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes. However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

• Korean Journal of Clinical Pharmacy
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• v.32 no.3
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• pp.215-225
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• 2022

Background: Patients with hematologic cancers have a risk of drug-related problems (DRPs) from medications associated with chemotherapy and supportive care. Although the role of oncology pharmacists has been widely documented in the literature, few studies have reported its impact on cost reduction. This study aimed to describe the activities of oncology pharmacists with respect to hematologic diseases and evaluate the associated cost avoidance. Methods: From January to July 2021, patients admitted to the department of hemato-oncology at Seoul National University, Bundang Hospital were studied. The activities of oncology pharmacists were reported by DRP type following the Pharmaceutical Care Network version 9.1 guidelines, and the acceptance rate was calculated. The avoided cost was estimated based on the cost of the pharmacy intervention, pharmacist manpower, and prescriptions associated with the intervention. Results: Pharmacists intervened in 584 prescriptions from 208 patients during the study period. The most prevalent DRP was "adverse drug event (possibly) occurring" (32.4%), followed by "effect of drug treatment not optimal" (28.6%). "Drug selection" (42.5%) and "dose selection" (30.3%) were the most common causes of DRPs. The acceptance rate of the interventions was 97.1%. The total avoidance cost was KRW 149,468,321; the net profit of the avoidance cost, excluding labor costs, was KRW 121,051,690; and the estimated cost saving was KRW 37,223,748. Conclusion: Oncology pharmacists identified and resolved various types of DRPs from prescriptions for patients with hematologic disease, by reviewing the prescriptions. Their clinical service contributed to enhanced patient safety and the avoidance of associated costs.

• Korean Journal of Clinical Pharmacy
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• v.28 no.3
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• pp.181-187
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• 2018

Background: Posaconazole is a broad-spectrum triazole antifungal agent and the most recommended prophylactic antifungal agent for patients with acute myeloid leukemia (AML) undergoing induction chemotherapy. In this study, we evaluated the status and effectiveness of posaconazole as a prophylactic antifungal agent in pediatric patients receiving induction chemotherapy for AML. Methods: We retrospectively reviewed the electronic medical records of 36 pediatric patients with AML (between January 2013 and September 2017) at the Yonsei University Health System. Invasive fungal disease (IFD) was assessed as the primary endpoint of prophylactic antifungal effect. The secondary endpoints were incidence of fever, persistent fever despite the use of broad-spectrum antibiotics for 72 h, alteration of antifungal agent, intensive care unit admission, and death within 100 days. Results: Among the 36 patients, 18 patients used posaconazole, 12 were treated with suspension formula, and 6 of them were treated with tablets. Eighteen patients did not use antifungal agents prophylactically. The mean number of days of posaconazole administration was $26.8{\pm}16days$. IFD occurred in 2/18 (11.1%) patients in the no prophylaxis group and in 1/18 (5.6%) patients in the posaconazole group (p=0.49). Conclusion: Posaconazole is expected to be useful for the prevention of IFD in pediatric patients with AML undergoing induction chemotherapy. Prospective studies of the effectiveness of posaconazole prophylaxis should be conducted in more pediatric patients in the future.

• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.138-145
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• 2018

Background: Presently, a multidisciplinary team of doctors, pharmacists, nurses, and dietitians provides patient education to impart information on chemotherapy. However, studies on multidisciplinary education satisfaction are inadequate. In this study, we aimed to contribute to the improvement of quality of multidisciplinary education counseling for patients with cancer by developing a satisfaction questionnaire and analyzing the satisfaction survey. Methods: A questionnaire was developed by an expert group, and the responses were recorded using the 5-point Likert scale. After conducting a pre-test, factor analysis was performed to evaluate validity. The reliability of the questionnaire was measured by Cronbach's alpha coefficient. A satisfaction survey was conducted by self-administration method. Results: Based on the results of factor analysis, factors can be divided into two parts: "overall education" and "each team member's education" (total 14 questions). The construct validity and reliability of the questionnaire are sufficiently high. Fifty-one patients took the survey between January 2, 2018 and January 20, 2018. Twenty-six (51%) patients responded that they were "very satisfied" and 22 (43.1%) patients responded that they were "satisfied". Conclusion: By developing a questionnaire on multidisciplinary education counseling for patients with cancer, it is possible to perform evaluation and research of cancer patient education. This study will contribute to the management and improvement of quality of multidisciplinary education.

• Korean Journal of Clinical Pharmacy
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• v.30 no.2
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• pp.92-101
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• 2020

Background: Delirium is a neuropsychiatric disorder characterized by sudden impairments in consciousness, attention, and perception. The evidence of successful pharmacological interventions for delirium is limited, and medication recommendations for managing delirium are not standardized. This study aimed to provide evidence of antipsychotics for symptomatic treatment of delirium in cancer patients receiving palliative care. Methods: We retrospectively reviewed adult cancer patients in palliative care who received antipsychotic delirium treatment at Severance Hospital between January 2016 and June 2019. The efficacy was evaluated primarily by resolution rates. The resolution of delirium was defined as neurological changes from drowsiness, confusion, stupor, sedation, or agitation to alertness or significant symptomatic improvements described in the medical records. The safety was studied primarily by adverse drug reaction incidence ratios. Results: Of the 63 enrolled patients, 60 patients were included in the statistical analysis and were divided into three groups based on which antipsychotic medication they were prescribed [quetiapine (n=27), haloperidol (n=25) and co-administration of quetiapine and haloperidol (n=8)]. The resolution ratio showed quetiapine to be more effective than haloperidol (p=0.001). No significant differences were seen in adverse drug reaction rates among the three groups (p=0.332). Conclusions: Quetiapine was considered the most effective medication for delirium, with no significant differences in adverse drug reaction rates. Therefore, quetiapine may be considered a first-line medication for treating delirium in cancer patients receiving palliative care. However, further studies comparing more diverse antipsychotics among larger populations are still needed.

• Korean Journal of Clinical Pharmacy
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• v.12 no.1
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• pp.7-12
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• 2002

Pharmacokinetic parameters and dosage of aminoglycosides (AGs) were studied retrospectively in 36 patients with neutropenic fever after stem cell transplantation in Seoul National University Hospital from July 1996 to June 2001. AGs pharmacokinetic parameters were calculated with steady-state peak and trough serum drug concentrations by the method of Sawchuk and Zaske et at. The calculated aminoglycosides volume of distribution and clearance were greater than population value $(0.36\pm0.06\;L/kg,\;116\pm32\;ml/min/1.73\;m^2,\;respectively)$. The average dosage of aminoglycosides required to maintain optimal serum AGs concentration was also greater than recommended dose in insert paper. The average dosage of amikacin was $11\pm2.1$ mg/kg every 12 hours (In case of tobramycin, $2.09\pm0.37$ mg/kg every 8 hours or $2.59\pm0.20$ mg/kg every 12 hours). The relationship between AGs volume of distribution and sex, serum albumin (g/dl), body mass index $(kg/m^2)$, body weight change $(\%)$, the amount of fluid inpu (ml/kg/day), the degree of hematocrit decrease $(\%)$ were studied respectively. Univariate anlysis revealed that body mass index $(kg/m^2)$, the amount of fluid input (ml/kg/day) and the degree of hematocrit decrease $(\%)$ had significant correlation with aminoglycosides volume of distribution. But sex, serum albumin, body weight change $(\%)$ had no significant correlation with aminoglycosides volume of distribution.

• Korean Journal of Clinical Pharmacy
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• v.33 no.2
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• pp.135-142
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• 2023

Background: Pharmacists communicate with a variety of healthcare experts to prevent medication errors. Situation-Background-Assessment-Recommendation (SBAR) is a tool used for concise and accurate communication. In 2018, we developed the pharmacy-SBAR (P-SBAR) to deliver pharmacists intervention more quickly and effectively through quality improvement activities. Objectives: This study evaluates the efficacy of P-SBAR on pharmacists' intervention activities before and after the implementation of P-SBAR applications. We assessed the impact of P-SBAR on reducing the burden of intervention work, promoting pharmacists' participation, and enhancing the acceptance rate. Methods: This is a retrospective study of the two groups before and after P-SBAR implementation. All pharmacists' intervention records during two periods (2016-2017 and 2019-2020) were extracted from the data warehouse system at Kyunghee University Hospital at Gangdong, Seoul. The outcome was the number of inpatients and pharmacists who participated in the prescription monitoring activity, the number of interventions, and the physicians' acceptance rate. Results: Although the total number of inpatients decreased (364,753 vs. 348,229), the number of pharmacists who participated in intervention activity increased (monthly mean: 15.8 vs. 18.0, p=0.001). The total number of interventions (2,767 vs. 4,389), the frequency of full acceptance (2,018 vs. 3,710), and the monthly acceptance rate increased significantly (73.8% vs. 83.8%, p<0.001). Conclusion: P-SBAR improved accessibility and convenience by digitalizing the intervention activities performed in an offline environment. Improvement in work burden and acceptance rate using P-SBAR is expected to contribute toward reducing medication errors.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1203-1209
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• 2018

Background/Aims: Adverse drug reaction (ADR) is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product. The present study was conducted in order to monitor the frequency and severity of ADR during antimicrobial therapy of septicemia. Methods: A prospective, observational, and noncomparative study was conducted over a period of 6 months on patients of septicemia admitted at a university hospital. Naranjo algorithm scale was used for causality assessment. Severity assessment was done by Hartwig severity scale. Results: ADRs in selected hospitalized patients of septicemia was found to be in 26.5% of the study population. During the study period, 12 ADRs were confirmed occurring in 9, out of 34 admitted patients. Pediatric patients experienced maximum ADRs, 44.4%. Females experienced a significantly higher incidence of ADRs, 66.7%. According to Naranjo's probability scale, 8.3% of ADRs were found to be definite, 58.3% as probable, and 33.3% as possible. A higher proportion of these ADRs, 66.7% were preventable in nature. Severity assessment showed that more than half of ADRs were moderate. Teicoplanin was found to be the commonest antimicrobial agent associated with ADRs, followed by gemifloxacin and ofloxacin. Conclusions: The incidence and severity of ADRs observed in the present study was substantially high indicating the need of extra vigilant during the antimicrobial therapy of septicemia.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.501-508
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• 2019

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and $NF-{\kappa}B$ p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of $CD4^+/CD8^+$ and the secretion of interleukin (IL)-2 and interferon-${\gamma}$, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3987-3992
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• 2014

Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7-AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (MMP) and the release of cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3 and increased cleaved PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin-induced apoptosis of SGC-7901 cells might be mediated through the mitochondria pathway, which gives the rationale for in vivo studies on the utilization of curcumin as a potential cancer therapeutic compound.