• Title/Summary/Keyword: drug-related side effects

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Anti-platelet role of Korean ginseng and ginsenosides in cardiovascular diseases

  • Irfan, Muhammad;Kim, Minki;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.44 no.1
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    • pp.24-32
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    • 2020
  • Cardiovascular diseases prevail among modern societies and underdeveloped countries, and a high mortality rate has also been reported by the World Health Organization affecting millions of people worldwide. Hyperactive platelets are the major culprits in thrombotic disorders. A group of drugs is available to deal with such platelet-related disorders; however, sometimes, side effects and complications caused by these drugs outweigh their benefits. Ginseng and its nutraceuticals have been reported to reduce the impact of thrombotic conditions and improve cardiovascular health by antiplatelet mechanisms. This review provides (1) a comprehensive insight into the available pharmacological options from ginseng and ginsenosides (saponin and nonsaponin fractions) for platelet-originated cardiovascular disorders; (2) a discussion on the impact of specific functional groups on the modulation of platelet functions and how structural modifications among ginsenosides affect platelet activation, which may further provide a basis for drug design, optimization, and the development of ginsenoside scaffolds as pharmacological antiplatelet agents; (3) an insight into the synergistic effects of ginsenosides on platelet functions; and (4) a perspective on future research and the development of ginseng and ginsenosides as super nutraceuticals.

EFFECTS OF ANTHOCYANOSIDE OLIGOMER ON MESOPIC CONTRAST SENSITIVITY IN MILD TO MODERATE MYOPIA

  • Seong Gong Je
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
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    • 2001.12a
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    • pp.52-60
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    • 2001
  • Purpose: We performed a randomized, double-blind, placebo-controlled trial in mild to moderate myopia patients to evaluate the benefit of taking a nutrient supplement containing anthocyanoside oligomers for improving nocturnal visiual function and/or clinical symptoms. Methods: The subjects included have refractive error between -lD(Diopters) $\~$-8D in both eyes, symptoms of decreased night vision and asthenopia based on the scoring result of a pre-structured questionnaire, and abnormal results of mesopic contrast sensitivity(MCS) screening test showing abnormal curve of contrast sensitivity in the middle and high frequency level, between 6.0 and 30.0 CPD(Cycles per degree) at mesopic condition(-2$\~$0 log cd/$m^2$). Total 60 people who qualified the criteria above were enrolled and the subjects were instructed to take the investigational product (anthocyanoside or placebo) twice daily for a 4 week period. The enrolled subjects were investigated for nocturnal vision performance by MCS and clinical symptoms at their first visit and re-evaluated at post-intervention (4 weeks later). MCS was measured and improvement of contrast threshold level according to each CPD was calculated by subtracting initial values from final values. Age, refractive error, and MCS were compared between the placebo and anthocyanoside. Results: After 4 weeks of drug administration 22 of the anthocyanoside group showed symptom improvement compared to 1 of the placebo group (p=0.000). Contrast sensitivity levels according to each CPD before and after drug treatment showed significant improvement in the anthocyanoside group but not in the placebo group. Mean MCS change of anthocyanoside group is 2.41$\pm$1.91 which showed significant improvement compared to -0.40$\pm$2.47 of the placebo group(p=0.000). MCS changes of anthocyanoside group showed significant improvement compared to placebo group in all levels of CPD(p<0.05). During our investigation none of the subjects complained of specific side effects related to anthocyanoside use. Conclusion: Our results show that under careful selection of people with significant symptoms and definite MCS abnormalities, anthocyanoside oligomers may improve the subjective symptoms and objective MCS results.

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Potentiation of the Cytotoxic Effects of Imatinib and TRAIL by Nonsteroidal Anti-inflammatory Drugs on Human Cancer Cells (비스테로이드소염제(Nonsteroidal Anti-inflammatory Drug, NSAID)에 의한 인간 암세포의 imatinib 및 TRAIL의 세포 독성 증강 기전 연구)

  • Moon, Hyun-Jung;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.30 no.8
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    • pp.661-671
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    • 2020
  • The resistance of cancer cells to anti-cancer drugs is the leading cause of chemotherapy failure. The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been gradually extended to cancer treatment through combination with anti-cancer drugs. In the current study, we investigated whether NSAIDs including celecoxib (CCB), 2,5-dimethyl celecoxib (DMC), and ibuprofen (IBU) could enhance the cytotoxic effects of imatinib and TNF-related apoptosis inducing ligand (TRAIL) on human cancer cells. We found that the NSAIDs potentiated TRAIL and imatinib cytotoxicity against human hepatocellular carcinoma (HCC) cell lines SNU-354, SNU-423, SNU-449, and SNU-475/TR and against leukemic K562 cells with high level of CD44 (CD44highK562), respectively. More specifically, CCB induced endoplasmic reticulum stress via up-regulation of ATF4/CHOP which is associated with the induction of autophagy against HCC and CD44high K562 cells. NSAID-induced autophagic activity accelerated TRAIL cytotoxicity of HCC cells through up- and down-regulation of DR5 and c-FLIP, respectively. The NSAIDs also potentiated imatinib-induced cytotoxicity and apoptosis through down-regulation of markers in CD44highK562 cells that express a stemness phenotype. Our results suggest that the ability of NSAIDs to induce autophagy could enhance the cytotoxicity of TRAIL and imatinib, leading to a reverse resistance to these drugs in the cancer cells. In conclusion, NSAIDs in combination with low-dose TRAIL or imatinib may constitute a novel clinical strategy that maximizes therapeutic efficacy of each drug and effectively reduces the toxic side effects.

Efficacy of two commonly used potentized homeopathic drugs, Calcarea carbonica and Lycopodium clavatum, used for treating polycystic ovarian syndrome (PCOS) patients: II. Modulating effects on certain associated hormonal levels

  • Das, Debarsi;Das, Indira;Das, Jayeeta;Koyal, Saroj Kumar;Khuda-Bukhsh, Anisur Rahman
    • CELLMED
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    • v.6 no.1
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    • pp.7.1-7.7
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    • 2016
  • In view of greater attention given to the incidence of Polycystic Ovarian Syndrome (PCOS) in women of reproductive age, particularly in urban and semi-urban population in India, research works in both the regimens of orthodox and complementary and alternative medicines have been rejuvenated in recent years. We report here relative efficacy of two potentized homeopathic remedies, Calcarea carbonica (Calc) and Lycopodium clavatum (Lyco) used traditionally for the removal of ovarian cysts. These drugs are most frequently used based on guiding symptoms of individual patients. Effects of either of these remedies on its ability of removing cysts, along with amelioration of certain other hormones and hormone-related parameters of PCOS, such as follicle stimulating hormone, luteinizing hormone, Estradiol, Testosterone (Free/Total), Dehydroepiandosterone, Prolactine, Progesterone (17- Hydroxyprogesterone), TSH including T3, T4, and Insulin were studied. The Insulin-related parameters like changes in fasting or postprandial glucose levels were also studied. The mentioned hormones play some- direct or indirect roles in causing irregular menstrual cycle and PCOS. The data collected at three fixation time points, namely, at 6, 12, and 18 months were considered. Results showed that out of 40 patients initially having PCOS, cysts were totally removed in 21 patients along with amelioration of other relevant symptoms. Both Calc and Lyco had amelioration of similar nature. Results of this study therefore validate safe and effective use of both Calc and Lyco in homeopathy, to patients with basic guiding symptoms for either drug, and can be recommended for patients with PCOS as they do not have any reported side-effects.

The Study on Identifying the Components of Community Pharmacy Externship Based on Korean Community Pharmacists' Consensus (약학교과과정의 개국약국실습 방향에 관한 연구)

  • Kim, Sung Hyun;Oh, Jung Mi
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.2
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    • pp.109-118
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    • 1999
  • The need for and components of a contemporary community pharmacy externship for pharmacy students have not been clearly identified in Korea. Mail survey was performed among 20 college of pharmacy deans and 800 community pharmacists to analyze the current status and develop a consensus regarding major focus area and criteria of community pharmacy externship to be implemented under the separation of dispensary from medical practice in year 2000. Mail survey yielded $80\%\;and\;23.5\%$ response rate for pharmacy school deans and community pharmacists, respectively. Of the 16 pharmacy schools that responded 14 said they have externship program in hospital pharmacy, and only 8 pharmacy schools responded of having externship program for community pharmacy. However, these community pharmacy programs lacked criteria and standard guideline for the externship. The results of survey revealed that community pharmacy externship program for students should be organized and directed toward developing expert knowledge and skills in pharmacy practice activities, clinical services, communications, pharmacy management, and professionalism. Pharmacy practice components should include competencies and skills in computer application, prescription processing, dispensing, pharmaceutical compounding, Narcotics Control Law application, maintenance and provision of drug information, and laws and regulations. Clinical service components should include the ability to identify patient's drug-related problems, provide long-term patient care and appreciate drug therapy services. Communication skills should be taught to effectively express his/her professional opinion, deduce the needs of others, utilize appropriate techniques and media to communicate ideas and conduct a patient interview and to obtain patient drug history. Pharmacy management skills should be taught to be efficient in medical insurance and drug control process. It was found that professionalism, morality, pharmacy practice experience, ability to provide clinical services, collect and provide drug information and regality are important criteria of preceptors. Externship sites should possess the ability to stock various drugs, access and provide diverse pharmacy services and should have private patient counseling area. Most pharmacists agreed that top 200 drugs' generic and brand name, indications, dosage, side effects, and contraindication should be instructed during the externship. It was also found that student and preceptor should be evaluated for their performances during the externship. This information will be incorporated into teaming objectives for students and to develop Academic Extemship Program Guidelines.

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The Effect of Nefopam on Postoperative Fentanyl Consumption: A Randomized, Double-blind Study

  • Moon, Jee Youn;Choi, Sang Sik;Lee, Shin Young;Lee, Mi Kyung;Kim, Jung Eun;Lee, Ji Eun;Lee, So Hyun
    • The Korean Journal of Pain
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    • v.29 no.2
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    • pp.110-118
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    • 2016
  • Background: Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug. The concomitant use of opioids and nefopam is believed to have many advantages over the administration of opioids alone for postoperative pain management. We conducted a randomized, double-blind study to determine the fentanyl-sparing effect of co-administration of nefopam with fentanyl for postoperative pain management via patient controlled analgesia (PCA). Methods: Ninety female patients who underwent laparoscopic total hysterectomy under general anesthesia were randomized into 3 groups, Group A, fentanyl $1,000{\mu}g$; Group B, fentanyl $500{\mu}g$ + nefopam 200 mg; and Group C, fentanyl $500{\mu}g$ + nefopam 400 mg, in a total volume of 100 ml PCA to be administered over the first 48 h postoperatively without basal infusion. The primary outcome was total fentanyl consumption during 48 h; secondary outcomes included pain scores and incidence of side effects. Results: Eighty-one patients were included in the analysis. The overall fentanyl-sparing effects of PCA with concomitant administration of nefopam during the first 48 h postoperatively were 54.5% in Group B and 48.9% group C. Fentanyl use was not significantly different between Groups B and C despite the difference in the nefopam dose. There were no differences among the three groups in terms of PCA-related side effects, although the overall sedation score of Group B was significantly lower than that of Group A. Conclusions: The concomitant administration of nefopam with fentanyl for postoperative pain management may allow reduction of fentanyl dose, thereby reducing the risk of opioid-related adverse effects.

Pharmacokinetics of talniflumate, a prodrug of niflumic acid, following oral administration to man

  • Kim, Hyun-Ji;Han, Yong-Hae;Chung, Suk-Jaeng;Lee, Min-Hwa;Shim, Chang-Koo
    • Archives of Pharmacal Research
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    • v.19 no.4
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    • pp.297-301
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    • 1996
  • Plasma profile of niflumic acid following oral administration of talniflumate tablets (Somalgen) was compared to that of niflumic acid tablets in man. Plasma niflumic acid was assayed by HPLC method. Plasma niflumic acid profile from the tainiflumate tablets was similar to that from the niflumic acid tablets resulting in no differences in $AUC, C_max, t_max$ and MRT. It demonstrates that talniflumate is a prodrug of niflumic acid, and undergoes extensive first-pass biotransformation to niflumic acid. However, plasma niflumic acid concentration at 30 min after tainiflumate dosing was significantly (p<0.05) higher than that of niflumic acid dosing. The more potent analgesic activity of talniflumate than niflumic acid might be related to this higher plasma drug concentration at the earlier phase. Considering that tainiflumate is less irritant to gastrointestinal mucosa than niflumic acid, talniflumate seems to be advantageous over niflumic acid in terms of activity and side effects.

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Epigenetic Silencing of CHOP Expression by the Histone Methyltransferase EHMT1 Regulates Apoptosis in Colorectal Cancer Cells

  • Kim, Kwangho;Ryu, Tae Young;Lee, Jinkwon;Son, Mi-Young;Kim, Dae-Soo;Kim, Sang Kyum;Cho, Hyun-Soo
    • Molecules and Cells
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    • v.45 no.9
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    • pp.622-630
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    • 2022
  • Colorectal cancer (CRC) has a high mortality rate among cancers worldwide. To reduce this mortality rate, chemotherapy (5-fluorouracil, oxaliplatin, and irinotecan) or targeted therapy (bevacizumab, cetuximab, and panitumumab) has been used to treat CRC. However, due to various side effects and poor responses to CRC treatment, novel therapeutic targets for drug development are needed. In this study, we identified the overexpression of EHMT1 in CRC using RNA sequencing (RNA-seq) data derived from TCGA, and we observed that knocking down EHMT1 expression suppressed cell growth by inducing cell apoptosis in CRC cell lines. In Gene Ontology (GO) term analysis using RNA-seq data, apoptosis-related terms were enriched after EHMT1 knockdown. Moreover, we identified the CHOP gene as a direct target of EHMT1 using a ChIP (chromatin immunoprecipitation) assay with an anti-histone 3 lysine 9 dimethylation (H3K9me2) antibody. Finally, after cotransfection with siEHMT1 and siCHOP, we again confirmed that CHOP-mediated cell apoptosis was induced by EHMT1 knockdown. Our findings reveal that EHMT1 plays a key role in regulating CRC cell apoptosis, suggesting that EHMT1 may be a therapeutic target for the development of cancer inhibitors.

Injection Formulation of Paclitaxel Employing Solid Lipid Nanoparticles (SLN) (고형지질나노입자를 이용한 파클리탁셀의 주사제 설계)

  • Choi, Sung-Up;Kim, Sun-Kyu;Lee, Jung-Min;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.33 no.4
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    • pp.319-322
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    • 2003
  • Many studies have been attempted to overcome the problems of paclitaxel related to the extremely low aqueous solubility of paclitaxel and the unexpected side-effects caused by $Cremophor^{\circledR}$ EL in a commercial paclitaxel formulation, $Taxol^{\circledR}$. In order to formulate a new delivery system suitable for intravenous administration without toxic excipients, in this study, paclitaxel was incorporated into solid lipid nanoparticles (Px-SLN) by hot homogenization technique using a microfluidizer. Particle size and zeta potential were measured by a Zetasizer. In vitro drug release experiment was performed by a dialysis diffusion method. Each Px-SLN or $Taxol^{\circledR}$ was intravenously administered to the male Sprague-Dawley rats at a dose of 5 mg/kg as paclitaxel. Blood samples were deproteinated with acetonitrile and assayed for paclitaxel by the validated HPLC/MS/MS method. Mean particle size and zeta potential were measured as 72.1 nm (< Polydispersity 0.3) and -41.5 mV, respectively. The content of paclitaxel in SLN was 1.42 mg/ml and the drug loading efficiency was $71.2{\pm}4.3%$. The $AUC_t$ of Px-SLN was 3.4-fold greater than that of $Taxol^{\circledR}$. The Px-SLN might be a promising candidate for an alternative formulation for the parenteral delivery of paclitaxel.

The effect of bisphosphonate discontinuation on the incidence of postoperative medication-related osteonecrosis of the jaw after tooth extraction

  • Kang, Sang-Hoon;Park, Se-Jin;Kim, Moon-Key
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.46 no.1
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    • pp.78-83
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    • 2020
  • Objectives: The discontinuation of bisphosphonate (BP) treatment before tooth extraction may induce medication-related osteonecrosis of the jaw (MRONJ). Whether the long-term discontinuation of BP treatment before tooth extraction affects the risk of developing MRONJ after tooth extraction or whether extended drug holidays induce systemic side effects remains unclear. The present study assessed the incidence of MRONJ among patients who underwent tooth extraction and did not discontinue BP therapy prior to the procedure. Materials and Methods: Patients were classified according to whether or not they discontinued BP therapy before tooth extraction. Differences in the incidence of MRONJ after tooth extraction were compared between the two groups using the chi-squared test. Results: The BP-continuation (BPC) and BP-discontinuation (BPDC) groups included 179 and 286 patients, respectively. One patient in the BPC group and no patients in the BPDC group developed MRONJ (P=0.385). The patients in the BPDC group stopped receiving BP therapy at a mean of 39.0±35.5 months prior to tooth extraction. Conclusion: The possibility of pre-existing MRONJ in the extraction area must be considered during the extraction procedure. Routine discontinuation of BP medications for several months before the extraction procedure should be carefully considered, as evidence of its efficacy in reducing the development of post-extraction MRONJ is limited.