• Title/Summary/Keyword: Drug-associated

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Efonidipine Inhibits JNK and NF-κB Pathway to Attenuate Inflammation and Cell Migration Induced by Lipopolysaccharide in Microglial Cells

  • Nguyen, Ngoc Minh;Duong, Men Thi Hoai;Nguyen, Phuong Linh;Bui, Bich Phuong;Ahn, Hee-Chul;Cho, Jungsook
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.455-464
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    • 2022
  • Efonidipine, a calcium channel blocker, is widely used for the treatment of hypertension and cardiovascular diseases. In our preliminary study using structure-based virtual screening, efonidipine was identified as a potential inhibitor of c-Jun N-terminal kinase 3 (JNK3). Although its antihypertensive effect is widely known, the role of efonidipine in the central nervous system has remained elusive. The present study investigated the effects of efonidipine on the inflammation and cell migration induced by lipopolysaccharide (LPS) using murine BV2 and human HMC3 microglial cell lines and elucidated signaling molecules mediating its effects. We found that the phosphorylations of JNK and its downstream molecule c-Jun in LPS-treated BV2 cells were declined by efonidipine, confirming the finding from virtual screening. In addition, efonidipine inhibited the LPS-induced production of pro-inflammatory factors, including interleukin-1β (IL-1β) and nitric oxide. Similarly, the IL-1β production in LPS-treated HMC3 cells was also inhibited by efonidipine. Efonidipine markedly impeded cell migration stimulated by LPS in both cells. Furthermore, it inhibited the phosphorylation of inhibitor kappa B, thereby suppressing nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 cells. Taken together, efonidipine exerts anti-inflammatory and anti-migratory effects in LPS-treated microglial cells through inhibition of the JNK/NF-κB pathway. These findings imply that efonidipine may be a potential candidate for drug repositioning, with beneficial impacts on brain disorders associated with neuroinflammation.

Drug Prescription Indicators in Outpatient Services in Social Security Organization Facilities in Iran

  • Afsoon Aeenparast;Ali Asghar Haeri Mehrizi;Farzaneh Maftoon;Faranak Farzadi
    • Journal of Preventive Medicine and Public Health
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    • v.57 no.3
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    • pp.298-303
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    • 2024
  • Objectives: The aim of this study was to estimate drug prescription indicators in outpatient services provided at Iran Social Security Organization (SSO) healthcare facilities. Methods: Data on all prescribed drugs for outpatient visits from 2017 to 2018 were extracted from the SSO database. The data were categorized into 4 main subgroups: patient characteristics, provider characteristics, service characteristics, and type of healthcare facility. Logistic regression models were used to detect risk factors for inappropriate drug prescriptions. SPSS and IBM Modeler software were utilized for data analysis. Results: In 2017, approximately 150 981 752 drug items were issued to outpatients referred to SSO healthcare facilities in Iran. The average number of drug items per outpatient prescription was estimated at 3.33. The proportion of prescriptions that included an injection was 17.5%, and the rate of prescriptions that included an antibiotic was 37.5%. Factors such as patient sex and age, provider specialty, type of facility, and time of outpatient visit were associated with the risk of inappropriate prescriptions. Conclusions: In this study, all drug prescription criteria exceeded the recommended limits set by the World Health Organization. To improve the current prescription patterns throughout the country, it would be beneficial to provide providers with monthly and annual reports and to consider implementing some prescription policies for physicians.

Factors influencing repeated suicide attempts among suicide attempters who visited the emergency room due to acute drug intoxication: a retrospective study (급성약물중독으로 응급의료센터를 내원한 자살시도자의 자살 재시도 영향요인: 후향적 연구)

  • In Ah Yun;Mi Yang Jeon
    • Journal of Korean Biological Nursing Science
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    • v.26 no.3
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    • pp.228-239
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    • 2024
  • Purpose: This retrospective study was conducted to identify factors associated with repeated suicide attempts by analyzing the electronic medical records of suicide attempters who visited emergency medical centers due to drug intoxication. Methods: Data from January 1, 2020 to December 31, 2021 were collected for this study and analyzed using SPSS/WIN 25.0. Results: In this study, the factors affecting repeated suicide attempts among individuals who visited the emergency medical center due to acute drug intoxication were the presence or absence of psychiatric diseases, the season of drug intoxication, and age. In order to identify the factors affecting repeated suicide attempts in those who presented with acute drug intoxication, logistic regression analysis was performed by inputting psychiatric diseases, season of drug intoxication, and age, all of which exhibited significant differences between those who did and did not attempt suicide again. The presence of psychiatric diseases (odds ratio [OR] = 1.99, 95% confidence interval [CI] = 1.04~3.80), intoxication occurring in the fall (vs. spring; OR = 3.35, 95% CI = 1.28~8.75), and age ≥ 65 (vs. those under the age of 18; OR = 12.96, 95% CI = 2.02~83.17). The regression model was found to be statistically significant (F = 30.01, p < .001), and the coefficient of determination of Cox and Snell, which represents the explanatory power of the model, was 12.0%. Conclusion: This study suggests that to prevent repeated suicide attempts, it is necessary to develop a tool to evaluate the risk of suicide, use it to evaluate the risk of suicide, and then manage individuals accordingly.

Adverse drug reactions reported over 5 years in a regional university hospital (일개 대학병원에서 경험한 5년간의 약물이상반응)

  • Jaechun Lee;Daehong Cho;Cheol-Woo Kim
    • Journal of Medicine and Life Science
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    • v.21 no.3
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    • pp.83-91
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    • 2024
  • Adverse drug reactions (ADRs) are closely associated with increased morbidity and mortality rates, prolonged hospitalization durations, and higher healthcare costs. This study aimed to estimate the incidence, clinical features, and reporting status of ADRs to improve the current ADR reporting system and prevent recurrent ADRs in hospitals. This retrospective study was conducted at a regional referral hospital. Patients diagnosed with ADRs over a 5-year period (2009-2014) were recruited for this study. An ADR was identified as an ADR-related diagnosis in a patient's medical record or an ADR registered through the in-hospital ADR reporting system. The incidence, culprit drug, clinical manifestations, reporting source, severity, related management, and recurrence rate were assessed. Among 1,112 patients, 1,375 ADR events were collected, an estimated 0.06% of the total number of patient visits. Diagnostic contrast agents (46.4%) were the most common culprit drugs, followed by antibiotics (22.0%), nonsteroidal anti-inflammatory drugs (9.9%), and opioids (4.5%). Skin reactions (67.5%) such as rashes and hives were the most frequent manifestations. Additional ADR-related medical attention was necessary in two thirds of cases. One hundred eighty ADR events (13.1%) were categorized as severe, and 19 patients (1.4%) experienced re-exposure to the culprit drugs. Four patients (0.3%) experienced fatal ADRs. Physicians were the most frequent ADR reporters in the in-hospital ADR reporting system. In conclusion, many ADR events may be overlooked, and re-exposure to causative drugs commonly occurs. Continuous education and maintenance of a reporting system may be important for preventing recurrent ADRs.

Pain medication and long QT syndrome

  • Klivinyi, Christoph;Bornemann-Cimenti, Helmar
    • The Korean Journal of Pain
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    • v.31 no.1
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    • pp.3-9
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    • 2018
  • Long QT syndrome is a cardiac repolarization disorder and is associated with an increased risk of torsades de pointes. The acquired form is most often attributable to administration of specific medications and/or electrolyte imbalance. This review provides insights into the risk for QT prolongation associated with drugs frequently used in the treatment of chronic pain. In the field of pain medicine all the major drug classes (i.e. NSAIDs, opioids, anticonvulsive and antidepressant drugs, cannabinoids, muscle relaxants) contain agents that increase the risk of QT prolongation. Other substances, not used in the treatment of pain, such as proton pump inhibitors, antiemetics, and diuretics are also associated with long QT syndrome. When the possible benefits of therapy outweigh the associated risks, slow dose titration and electrocardiography monitoring are recommended.

Prevalence of Drug-resistances in Patients with Pulmonary Tuberculosis and Its Association with Clinical Characteristics at One Tertiary Referral Hospital in Pusan, Korea (부산지역 한 3차 병원으로 내원한 폐결핵 환자에서 약제 내성률과 예측인자간의 연관성)

  • Son, Choon-Hee;Yang, Doo-Kyung;Rho, Mee-Sook;Jeong, Jin-Sook;Lee, Hyuck;Lee, Ki-Nam;Choi, Pil-Jo;Lee, Soo-Keol;Chang, Kwang-Yul;Choi, Ik-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.5
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    • pp.416-425
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    • 2001
  • Background : The incidence of drug-resistant tuberculosis has recently decreased in Korea. However, it is still one of the major obstacles in treating pulmonary tuberculosis. This study was performed to determine the prevalence and clinical characteristics associated with drug-resistance in pulmonary tuberculosis at the tertiary referral hospital in Pusan, Korea. Methods : The medical records of 138 patients, who had been diagnosed as active pulmonary tuberculosis were retrospectively reviewed, and results of drug susceptibility from May 1997 to June 2000. The relationships among those with a history of previous tuberculosis treatment, the extent of lung involvement, the presence of cavities on the initial chest X-ray films and patterns of drug resistance were analyzed. Results : The total number of patients who had drug resistance to at least one drug was 55(39.9%). Among them 34(24.6%) had resistance to isoniazid(INH) and rifampin(RFP). There was drug resistance in 20(22%) of 91 patients without previous tuberculosis therapy, and among them 9(9.9%) were multi-drug resistant. Thirty-two(74.5%) out of 47 patients with previous therapy were drug-resistant and 25(53.2%) were multidrug resistant. For all 138 patients, resistance to INH was the most common(34.1%), followed by RFP(26.1%) and ethambutol(EMB)(14.5%). Drug resistance to INH, RFP, PZA and streptomycin(SM) were independently associated with a history of previous treatment(odds ratio; 9.43, 9.09, 8.93 and 21.6 respectively, p<0.01). The extent of lung involvement on the chest films was significantly associated with the drug resistance to INH and RFP(odds ratio; 2.12 and 2.40 respectively, p<0.01). The prevalence of drug resistance to RFP, INH and RFP was significantly more common in patients with a cavitary lesion on the chest films by multivariate analysis(odds ratio; 4.17 and 4.81 respectively, p<0.05). Conclusion : This study revealed that patients with a prior treatment history for pulmonary tuberculosis, and the presence of a cavitary lesion on chest films had a higher prevalence of anti-tuberculosis drug resistance. A very careful clinical and microbiological examination is needed for patients with such characteristics.

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Sex Differences in Cancer: Epidemiology, Genetics and Therapy

  • Kim, Hae-In;Lim, Hyesol;Moon, Aree
    • Biomolecules & Therapeutics
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    • v.26 no.4
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    • pp.335-342
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    • 2018
  • The incidence and mortality of various cancers are associated with sex-specific disparities. Sex differences in cancer epidemiology are one of the most significant findings. Men are more prone to die from cancer, particularly hematological malignancies. Sex difference in cancer incidence is attributed to regulation at the genetic/molecular level and sex hormones such as estrogen. At the genetic/molecular level, gene polymorphism and altered enzymes involving drug metabolism generate differences in cancer incidence between men and women. Sex hormones modulate gene expression in various cancers. Genetic or hormonal differences between men and women determine the effect of chemotherapy. Until today, animal studies and clinical trials investigating chemotherapy showed sex imbalance. Chemotherapy has been used without consideration of sex differences, resulting in disparity of efficacy and toxicity between sexes. Based on accumulating evidence supporting sex differences in chemotherapy, all clinical trials in cancer must incorporate sex differences for a better understanding of biological differences between men and women. In the present review, we summarized the sex differences in (1) incidence and mortality of cancer, (2) genetic and molecular basis of cancer, (3) sex hormones in cancer incidence, and (4) efficacy and toxicity of chemotherapy. This review provides useful information for sex-based chemotherapy and development of personalized therapeutic strategies against cancer.

SETDB1 mediated FosB expression increases the cell proliferation rate during anticancer drug therapy

  • Na, Han-Heom;Noh, Hee-Jung;Cheong, Hyang-Min;Kang, Yoonsung;Kim, Keun-Cheol
    • BMB Reports
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    • v.49 no.4
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    • pp.238-243
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    • 2016
  • The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy.

Immunostimulant and Anti-Tumor Activity of Crude Extracts of Galium aparine L. (팔선초 물 추출물의 면역자극 및 항종양 활성)

  • Yoon, Taek-Joon;Lee, Chang-Kwon;Park, Tae-Kyu;Lee, Kwang-Ho
    • Korean Journal of Pharmacognosy
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    • v.36 no.4 s.143
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    • pp.332-337
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    • 2005
  • We here demonstrate the evidence of increased anti-tumor and immunostimulating activities of crude extracts (GAL) from Galium. aparine L. In experimental lung metastasis of colon26-M3.1 carcinoma or B16-BL6 melanoma cells, prophylactically intravenous (i.v) administration of GAL significantly inhibited lung metastasis in a dose-dependant manner. In an in vitro cytotoxicity analysis, GAL at the concentration up to $500\;{\mu}g/ml$ did not affect the growth of B16-BL6 melanoma cells. In contrast, GAL showed the enhancement of splenocyte proliferating activity in a dose-dependent manner. Peritoneal macrophages stimulated with GAL produced various cytokines such as $1L-1{\beta},\;TNF-{\alpha},\;IFN-{\gamma}$ and IL-12. These data suggest that GAL has an antitumor activity to inhibit tumor metastasis, and its antitumor effects is associated with activation of nonspecific immnune related cells.

The Surgery of Pulmonary Tuberculosis: 163 cases experience (폐결핵 수술: 163례 보고)

  • 박창권
    • Journal of Chest Surgery
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    • v.21 no.1
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    • pp.109-115
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    • 1988
  • With the decreasing incidence of new cases and the highly effective results with antituberculous drug therapy, there is a marked decline in the need for surgery which was formerly such an important part in the successful program of management of this disease. During the period of two years and a half from Jun. 1984 to Dec. 1986, this study represents an analysis of 163 cases of several surgical management for eventual control of pulmonary tuberculosis at National Kon-ju tuberculosis Hospital. 1. Mode of surgical treatment was: Resection; 123 cases [Pneumonectomy: 83, lobectomy: 35, lobectomy plus segmentectomy; 4 segmentectomy: 1], thoracoplasty: 20 and others: 20. 2. Age distribution ranged 16and 68 with average of 34 years. Male and female ratio was 1.2: 1. 3. Surgical indications were: totally destroyed lung; 64, Destroyed lobe of segment; 13, cavity positive sputum; 10, cavity c negative Sputum; 6, Bronchostenosis c atelectasis; 2, empyema c or s BPF; 46, Aspergilloma; 8, Questions of Associated tumor; 4 and other 5. 4. Incidence of Complications was 10.4% and the mortality was 5.5 percent. The cause of mortality were analyzed. The main causes of death were respiratory insufficiency; 4, fulminant hepatitis; 1, hemorrhage; 1 and unknown; 1 in pneumonectomy, and asphyxia; 1 in lobectomy and sepsis; 1 in other procedure. 5. Conversion rare of positive sputum to negative state related to resectional surgery was 91.5%. In pneumonectomy, drug resistant group preoperatively showed 88.1% conversion rate postoperatively and drug sensitive group showed that 100% conversion rate. In lobectomy, both drug resistant and sensitive groups showed that 100% conversion rate postoperatively.

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